B-LACTOGLOBULIN致敏性降低的免疫学机制
摘要
牛乳β-乳球蛋白(β-lg)是胎儿出生后遇到的第一个外来过敏原,并且它是导致牛乳蛋白过敏的主要过敏原。酶水解作用可以导致β-lg空间三维结构的变化,但是该酶诱导结构变化对其致敏性的意义还不清楚。为了探明水解作用对β-lg致敏性或者抗原性的影响,本实验利用小鼠动物模型研究了水解作用对β-lg致敏性的影响。
本研究主要从以下几个方面探讨了水解降低β-lg致敏性的机制:脾淋巴细胞增殖实验;ELISA方法检测血清和小肠液中的IgE水平;利用试剂盒检测血浆中组胺水平;还检测了脾淋巴细胞培养上清中各种细胞因子(IL-2,IL-4,IL-10,IFN-γ)水平,脾淋巴细胞表面抗原(CD4+,CD8+,CD3+,CD19+)。
脾细胞是主要的淋巴细胞,本试验通过淋巴细胞增殖试验来研究β-lg,和β-lg水解物在体内免疫调节作用,不加ConA组数据表明,和β-lg水解物以及OVA组相比,β-lg能够显著刺激脾淋巴细胞增殖(分别为p=0.01, p=0.001),β-lg水解物和OVA相比,差异也是极显著的。(p=0.002)。并且,加ConA的各组与不加ConA的实验组相比有相同的趋势。例如β-lg组和酶β-lg水解物组以及OVA组相比,差异都显著(分别为p=0.007,p=0.001)。除此之外,添加ConA和不添加ConA实验组相比,整体趋势是不添加ConA组要比添加ConA组有较大的刺激性(p=0.508β-lg vsβ-lg+ConA)。
使用ELISA方法检测了小鼠血清和小肠液IgE抗体水平,结果表明β-lg组小鼠血清IgE水平要高于β-lg水解物组小鼠,而小肠液中IgE水平和血清IgE水平变化趋势一致,但是整体水平要高于血清。
在本试验中,血浆组胺是通过ELISA试剂盒检测的,结果表明,灌胃β-lg组小鼠血浆组胺水平显著高于酶解β-lg组和OVA组(分别为p=0.002,p=0.000)。酶解β-lg组血浆组胺水平也显著高于OVA组(p=0.007)。
本实验还检测了脾淋巴细胞培养上清中Th1型细胞因子(IL-2,IFN-γ)和Th2型细胞因子(IL-4,IL-10)。在脾细胞培养液中加入β-lg和β-lg水解物,和对照组细胞相比,对其细胞因子分泌水平影响不大,差异不显著。但是,在有ConA存在时,β-lg显著的刺激了IL-4,IL-10,IFN-γ的分泌。除此之外,由于β-lg的存在,抑制了ConA刺激的脾细胞中IL-2的表达,但是和空白组相比差异不显著。另一方面,β-lg水解物增加了IFN-γ在ConA刺激的脾细胞中的表达,但是对其他细胞因子的分泌没有影响。这些结果说明,β-lg水解物不但能够抑制脾细胞增殖,还对细胞因子的分泌有调节作用。
创新点:
对水解作用对β-lg致敏性的影响进行了系统的研究。利用β-lg作为致敏原,balb/c小鼠为动物模型,研究血清IgE,血浆组胺水平,细胞因子水平,细胞表面抗原,解释了水解作用降低β-lg致敏性的免疫学机制,为信号转导、体液免疫等进一步研究过敏降低机制提供了参考。
Bovineβ-lactoglobulin (β-lg) is one of the first foreign antigens encountered by a newborn child, and it is the major allergen causing cow’s milk allergy. Hydrolysis can cause changes to the protein structure, but the significance of hydrolysis-induced changes for immunogenicity or allergenicity is not known. To clarify how hydrolysis affects allergenicity and immunogenicity, the sensitization ofβ-lg by enzymatic hydrolysis was evaluated in this paper using the mouse model.
This study explored the mechanism to reduce the sensitization of hydrolysisβ-lg by the following aspects: spleens lymphocyte proliferation test; IgE levels in serum and intestinal tracts by ELISA method; determination of plasma histamine levels using kits; various cytokines in the supernatants of spleen cells (IL-2, IL-4, IL-10, IFN-γ), spleen lymphocyte surface antigen (CD4+, CD8+, CD3+, CD19+).
Spleens were the main lymphocyte, and this article researched immunomodulating effect ofβ-lg and enzymatic hydrolysisβ-lg in vitro by measuring their impacts on lymphocyte proliferation which were expressed as a stimulation index (SI) and was evaluated with and without suboptimal concentration (0.5 mg/ml) of ConA (Fig 2). The results of absence ConA showed thatβ-lg could significantly stimulate lymphocyte proliferation than enzymatic hydrolysisβ-lg as well as OVA (p=0.01, p=0.000 respectively), the result of comparing enzymatic hydrolysisβ-lg to OVA also showed obvious difference (p=0.002). Furthermore, the ConA present group had the same trend with the absence group. Theβ-lg group showed significant difference to enzymatic hydrolysisβ-lg as well as OVA (p=0.007, p=0.001, respectively) but without obvious difference compared to enzymatic hydrolysisβ-lg (p=0.061). Besides, the whole trend between absence ConA and present ConA was that the absence ConA group showed a lower stimulation than present ConA group, but the difference was not significant (p=0.508β-lg vsβ-lg+ConA).
Enzyme-linked immunosorbent assay (ELISA) methods were developed to quantify the antibody level in balb/c mouse by gavage ofβ-lg and enzymatic hydrolysisβ-lg with dosages of 10mg/ml, 10mg/ml, respectively. The serum IgE level inβ-lg group and intestinal fluid samples were higher than those in enzymatic hydrolysis group, but the total IgE level in intestinal fluid samples is higher than serum IgE.
Plasma histamine levels were determined by an ELISA kit and the results indicated that the histamine level of mice challenged intragastrically withβ-lg showed significant high level than enzymatic hydrolysisβ-lg and OVA (p=0.002, p=0.000, respectively) (Fig 4). The histamine levels of enzymatic hydrolysisβ-lg also showed significant high level than OVA (p=0.007).
This paper also examined the secretion of Th1 (IL-2, IFN-γ) and Th2 (IL-4, IL-10) cytokines by resting splenocytes, and the results indicated that nativeβ-lg and enzymatic hydrolysisβ-lg had no effect on the secretion of Th1 (IL-2, IFN-γ) and Th2 (IL-4, IL-10) cytokines, while nativeβ-lg significantly stimulated the secretion of IL-2 and IFN-γwith ConA-induced spleens, whereas enzymatic hydrolysisβ-lg significantly increased IFN-γsecretion.These results suggest that hydrolysing theβ-lg not only eliminates its inhibiting effect on the proliferation of splenocytes in the presence of ConA but also modifies its effect on cytokine secretion.
Innovation
This paper systemically detected the serum IgE, plasma histamine levels, cytokine levels and cell surface antigens, usingβ-lg as allergens, balb/c mice as animal model, firstly from the perspective of immunology, and explained the immunological mechanism of lower sensitization of hydrolysisβ-lg, which provided references for the signal transduction, humoral immunity etc.
本研究主要从以下几个方面探讨了水解降低β-lg致敏性的机制:脾淋巴细胞增殖实验;ELISA方法检测血清和小肠液中的IgE水平;利用试剂盒检测血浆中组胺水平;还检测了脾淋巴细胞培养上清中各种细胞因子(IL-2,IL-4,IL-10,IFN-γ)水平,脾淋巴细胞表面抗原(CD4+,CD8+,CD3+,CD19+)。
脾细胞是主要的淋巴细胞,本试验通过淋巴细胞增殖试验来研究β-lg,和β-lg水解物在体内免疫调节作用,不加ConA组数据表明,和β-lg水解物以及OVA组相比,β-lg能够显著刺激脾淋巴细胞增殖(分别为p=0.01, p=0.001),β-lg水解物和OVA相比,差异也是极显著的。(p=0.002)。并且,加ConA的各组与不加ConA的实验组相比有相同的趋势。例如β-lg组和酶β-lg水解物组以及OVA组相比,差异都显著(分别为p=0.007,p=0.001)。除此之外,添加ConA和不添加ConA实验组相比,整体趋势是不添加ConA组要比添加ConA组有较大的刺激性(p=0.508β-lg vsβ-lg+ConA)。
使用ELISA方法检测了小鼠血清和小肠液IgE抗体水平,结果表明β-lg组小鼠血清IgE水平要高于β-lg水解物组小鼠,而小肠液中IgE水平和血清IgE水平变化趋势一致,但是整体水平要高于血清。
在本试验中,血浆组胺是通过ELISA试剂盒检测的,结果表明,灌胃β-lg组小鼠血浆组胺水平显著高于酶解β-lg组和OVA组(分别为p=0.002,p=0.000)。酶解β-lg组血浆组胺水平也显著高于OVA组(p=0.007)。
本实验还检测了脾淋巴细胞培养上清中Th1型细胞因子(IL-2,IFN-γ)和Th2型细胞因子(IL-4,IL-10)。在脾细胞培养液中加入β-lg和β-lg水解物,和对照组细胞相比,对其细胞因子分泌水平影响不大,差异不显著。但是,在有ConA存在时,β-lg显著的刺激了IL-4,IL-10,IFN-γ的分泌。除此之外,由于β-lg的存在,抑制了ConA刺激的脾细胞中IL-2的表达,但是和空白组相比差异不显著。另一方面,β-lg水解物增加了IFN-γ在ConA刺激的脾细胞中的表达,但是对其他细胞因子的分泌没有影响。这些结果说明,β-lg水解物不但能够抑制脾细胞增殖,还对细胞因子的分泌有调节作用。
创新点:
对水解作用对β-lg致敏性的影响进行了系统的研究。利用β-lg作为致敏原,balb/c小鼠为动物模型,研究血清IgE,血浆组胺水平,细胞因子水平,细胞表面抗原,解释了水解作用降低β-lg致敏性的免疫学机制,为信号转导、体液免疫等进一步研究过敏降低机制提供了参考。
Bovineβ-lactoglobulin (β-lg) is one of the first foreign antigens encountered by a newborn child, and it is the major allergen causing cow’s milk allergy. Hydrolysis can cause changes to the protein structure, but the significance of hydrolysis-induced changes for immunogenicity or allergenicity is not known. To clarify how hydrolysis affects allergenicity and immunogenicity, the sensitization ofβ-lg by enzymatic hydrolysis was evaluated in this paper using the mouse model.
This study explored the mechanism to reduce the sensitization of hydrolysisβ-lg by the following aspects: spleens lymphocyte proliferation test; IgE levels in serum and intestinal tracts by ELISA method; determination of plasma histamine levels using kits; various cytokines in the supernatants of spleen cells (IL-2, IL-4, IL-10, IFN-γ), spleen lymphocyte surface antigen (CD4+, CD8+, CD3+, CD19+).
Spleens were the main lymphocyte, and this article researched immunomodulating effect ofβ-lg and enzymatic hydrolysisβ-lg in vitro by measuring their impacts on lymphocyte proliferation which were expressed as a stimulation index (SI) and was evaluated with and without suboptimal concentration (0.5 mg/ml) of ConA (Fig 2). The results of absence ConA showed thatβ-lg could significantly stimulate lymphocyte proliferation than enzymatic hydrolysisβ-lg as well as OVA (p=0.01, p=0.000 respectively), the result of comparing enzymatic hydrolysisβ-lg to OVA also showed obvious difference (p=0.002). Furthermore, the ConA present group had the same trend with the absence group. Theβ-lg group showed significant difference to enzymatic hydrolysisβ-lg as well as OVA (p=0.007, p=0.001, respectively) but without obvious difference compared to enzymatic hydrolysisβ-lg (p=0.061). Besides, the whole trend between absence ConA and present ConA was that the absence ConA group showed a lower stimulation than present ConA group, but the difference was not significant (p=0.508β-lg vsβ-lg+ConA).
Enzyme-linked immunosorbent assay (ELISA) methods were developed to quantify the antibody level in balb/c mouse by gavage ofβ-lg and enzymatic hydrolysisβ-lg with dosages of 10mg/ml, 10mg/ml, respectively. The serum IgE level inβ-lg group and intestinal fluid samples were higher than those in enzymatic hydrolysis group, but the total IgE level in intestinal fluid samples is higher than serum IgE.
Plasma histamine levels were determined by an ELISA kit and the results indicated that the histamine level of mice challenged intragastrically withβ-lg showed significant high level than enzymatic hydrolysisβ-lg and OVA (p=0.002, p=0.000, respectively) (Fig 4). The histamine levels of enzymatic hydrolysisβ-lg also showed significant high level than OVA (p=0.007).
This paper also examined the secretion of Th1 (IL-2, IFN-γ) and Th2 (IL-4, IL-10) cytokines by resting splenocytes, and the results indicated that nativeβ-lg and enzymatic hydrolysisβ-lg had no effect on the secretion of Th1 (IL-2, IFN-γ) and Th2 (IL-4, IL-10) cytokines, while nativeβ-lg significantly stimulated the secretion of IL-2 and IFN-γwith ConA-induced spleens, whereas enzymatic hydrolysisβ-lg significantly increased IFN-γsecretion.These results suggest that hydrolysing theβ-lg not only eliminates its inhibiting effect on the proliferation of splenocytes in the presence of ConA but also modifies its effect on cytokine secretion.
Innovation
This paper systemically detected the serum IgE, plasma histamine levels, cytokine levels and cell surface antigens, usingβ-lg as allergens, balb/c mice as animal model, firstly from the perspective of immunology, and explained the immunological mechanism of lower sensitization of hydrolysisβ-lg, which provided references for the signal transduction, humoral immunity etc.
引文
李树芹,李文,李宁等. 2000.转基因技术改变牛乳成分的最新进展.中国乳品工业. 4:39-42.
李欣,陈红兵.2005.过敏原在食品加工中的变化.食品工业. 1:50-52.
赵新淮.1994.蛋白质水解物水解度的测定.食品科学.11:65～67
Adel-Patient K, Creminon C, Bernard H, Clement G, Negroni L, Frobert Y, Grassi J, Wal JM, Chatel JM. 2000. Evaluation of a high IgE-responder mouse model of allergy to bovine beta- lactoglobulin (β-lg): development of sandwich immunoassays for total and allergen-specific IgE, IgG1 and IgG2a inβ-lg sensitized mice. J Immunol Methods. 235(1-2): 21-32.
Andre F, Andre C, Colin L, Cacaraci F, Cavagna S. 1994. Role of new allergens and of allergens consumption in the increased incidence of food sensitizations in France. Toxicology. 93(1): 77-83.
Anema A, Ritmeijer K. 2005. Treating HIV/AIDS and leishmaniasis coinfection in Ethiopia. CMAJ. 172(11):1434-1435.
Anguita G, Martin R, Garcia T, Morales P, Haza AI, Gonzalez I, Sanz B, Hernandez PE. 1997.
A competitive enzyme-linked immunosorbent assay for detection of bovine milk in ovine and caprine milk and cheese using a monoclonal antibody against bovine beta-casein. J Food Prot. 60:64–66.
Anveden-Hertzberg L, Finkel Y, Sandstedt B, Karpe B. 1996. Proctocolitis in exclusively breast-fed infants. Eur J Pediatr. 155(6):464-467.
Arshad SH, Tariq SM, Matthews S, Hakim E. 2001. Sensitization to common allergens and its association with allergic disorders at age 4 years: a whole population birth cohort study. Pediatrics. 108(2):E33.
Asselin J, Hebert J, Amiot J. 1989. Effects of in vitro proteolysis on the allergenicity of major whey proteins,J Food Sci. 54:1037–1039.
Astwood JD, Leach JN, Fuchs RL. 1996. Stability of food allergens to digestion in vitro. Nat Biotechnol. 14(10): 1269-1273.
Baehler P, Chad Z, Gurbindo C, Bonin AP, Bouthillier L, Seidman EG. 1996. Distinct patterns of cow’s milk allergy in infancy defined by prolonged, two-stage double blind, placebo-controlled food challenges. Clin Exp Allergy. 26(3):254-61.
Baumgarth N. 2000. A two-phase model of B-cell activation. Immunological Reviews. 176: 171–180.
Beavis AJ, Pennline KJ. 1994. Simultaneous measurement of fivecell surface antigens by five-colour immunofluorescence. Cytometry. 15:371-376.
Belloque J, and Smith GM. 1998. Thermal denaturation ofβ-lactoglobulin. A 1H NMR study. J Agric Food Chem. 46:1805–1813.
Bernard H, Creminon C, Yvon M, Wal JM. 1998. Specificity of the human IgE response to the different purified caseins in allergy to cow’s milk proteins. Int Arch Allergy Immunol. 115 (3): 235–244.
Bertrand-Harb C, Baday A, Dalgalarrondo M, Chobert JM, Haertle T.2002. Nahrung 46:283–289.
Bevilacqua C, Martin P, Candalh C, Fauquant J, Piot M, Roucayrol AM, Pilla F, Heyman M. 2001. Goat’s milk of defective alpha (s1)-casein genotype decreases intestinal and systemic sensitization to beta-lactoglobulin in guinea pigs. J Dairy Res. 68 (2):217–227.
Black CL, Reynolds EC.1998. An ELISA for a multi-phosphorylated peptide, as1-casein (59-79). J Immunol Methods. 214:63–71.
Blais BW, Gaudreault M, Phillippe LM. 2003 Multiplex enzyme immunoassay system for the simultaneous detection of multiple allergens in foods. Food Control. 14:43–47.
Blaise F, GagnéM, Salazar S, Salazar S, Trottier, Hansen PD. 2003. Expmentally-induced feminisation of freshwater mussels after long-term exposure to a municipal effluent, Fresenius Environ Bull. 12:865–870.
Bock SA, Sampson HA, Atkins FM, Zeiger RS, Lehrer S, Sachs M. 1988. Doubleblind placebo-controlled food challenge (DBPCFC) as an office procedure: a manual. J Allergy Clin Immunol. 82(6):986-997.
Bonomi F, Fiocchi A, Frokiaer H, Gaiaschi A, Iametti S, Poiesi C, Rasmussen P, Restani P, Rovere P. 2003. Reduction of immunoreactivity of bovine beta-lactoglobulin upon combined physical and proteolytic treatment,J Dairy Res. 70:51–59.
Brix S, Bovetto L, Fritsche R, Barkholt V, Frokiaer H. 2003. Immunostimulatory potential of beta-lactoglobulin preparations: Effects caused by endotoxin contamination. Journal of Allergy and Clinical Immunology. 112(6): 1216–1222.
Brix S, Christensen HR, Barkholt V, Frokiaer H. 2005. Effect of Maternal Dietary Cow's Milk on the Immune Response to Beta-Lactoglobulin in the Offspring: A Four-Generation Study in Mice. Int Arch Allergy Immunol. 136(3): 250-257.
Brownlow S, Cabral JHM, Cooper R, Flower DR, Yewdall SJ, Polikarpov I, North ACT, Sawyer L. 1997. Bovineβ-lactoglobulin at 1.8 angstrom resolution—still an enigmatic lipocalin. Structure 5:481–495.
Burczynski FJ, Moran JB, Cai ZS, Forker EL.1990. Beta-lactoglobulin enhances the uptake of free palmitate by hepatocyte monolayers: the relative importance of diffusion and facilitated dissociation. Can J Physiol Pharmacol. 68(2): 201-216.
Busse PJ, Jarvinen KM, Vila L, Beyer K, Sampson HA. 2002. Identification of sequential IgE-binding epitopoes on bovine alpha (S2) casein in cow’s milk allergic patients. Int Arch Allergy Immunol. 129 (1): 93–96.
Canani RB, Ruotolo S, Auricchio L, Caldore M, Porcaro F, Manguso F. 2007. Diagnostic accuracy of the atopy patch test in children with food allergy-related gastrointestinal symptoms. Allergy. 62(7):738-43.
Cantani A, Lucenti P. 1997. Natural history of soy allergy and/or intolerance in children, and clinical use of soy-protein formulas. Pediatr Allergy Immunol. 8(2):59-74.
Casal HL, Kohler U, Mantsch HH.1988. Structural and conformational changes of beta- lactoglobulin B: an infrared spectroscopic study of the effect of pH and temperature. Biochim Biophys Acta. 957(1): 11-20.
Cavagni G, Plebani A, Restani P, Marini S, Gardenghi M, Poiesi C, Duse M, Ugazio AG. 1994.
Allergy to cow’s milk proteins in childhood: the author’s personal experience and new diagnostic and therapeutic proposals. Pediatr Med Chir. 16 (5):413–419.
Cocco RR, Jarvinen KM, Sampson HA, Beyer K. 2003. Mutational analysis of major sequential IgE-binding epitopes in alphas1-casein, a major cow’s milk allergen. J Allergy Clin Immunol. 112 (2):433–437.
Creamer LK, Bienvenue A, Nilsson H, Paulsson M, van Wanroij M, Lowe EK, Anema SG, Boland MJ, Jimenez-Flores R. 2004. Heat-Induced Redistribution of Disulfide Bonds in Milk Proteins. 1. Bovine beta-Lactoglobulin. J Agric Food Chem. 52(25): 7660-7668.
Cross ML, Gill HS. 1999. Modulation of immune function by a modified bovine whey protein concentrate, Immunology and Cell Biology. 77: 345-350.
Cross ML, Stevenson LM, Gill HS. 2001. Anti-allergy properties of fermented foods: an important immunoregulatory mechanism of lactic acid bacteria. International Immuno pharmacology. 1: 891-901.
Dahlgren UI, Wold AE, Hanson LA, Midtvedt T. 1991. Secretory antibody response against bacterial antigens and food proteins. Immunol Res. 10(3-4): 437-440.
Davis PJ, Williams SC. 1998. Protein modification by thermal processing. Allergy 53(46 Suppl): 102-105.
Dearman RJ, Caddick H, Stone S, Basketter DA, Kimber I. 2001. Characterization of antibody responses induced in rodents by exposure to food proteins: influence of route of exposure. Toxicology. 167(3): 217-231.
Dearman RJ, Kimber I. 2001. Determination of protein allergenicity: studies in mice. Toxicol Lett. 120(1-3): 181-186.
del Val G, Yee BC, Lozano RM, Buchanan BB, Ermel RW, Lee YM, Frick OL .1999.
Thioredoxin treatment increases digestibility and lowers allergenicity of milk. J Allergy Clin Immunol. 103(4): 690-697.
Diane Saint-Sauveura, Sylvie F. Gauthiera, Yvan Boutinb, Alicia Montonia. 2008.
Immunomodulating properties of a whey protein isolate, its enzymatic digest and peptide fractions. International Dairy Journal. 18: 260-270.
Docena G, Rozenfeld P, Fernándea R, Fassati CA.2002. Evaluation of the residual antigenicityand allergenicity of cow’s milk substitutes by in vitro tests. Allergy. 57(2): 83-91.
Docena GH, Fernandez R, Chirdo FG, Fossati CA. 1996. Identification of casein as the major allergenic and antigenic protein of cow’s milk. Allergy. 51 (6):412–416.
Dupont D, Rolet-Repecaud O, Muller-Renaud S. 2004. Determination of the heattreatment undergone by milk by following the denaturation ofα-lactalbumin with a biosensor J Agric Food Chem. 52:677–681.
Ehn BM, Ekstrand B, Bengtsson U, Ahlstedt S.2004. Modification of IgE binding during heat processing of the cow's milk allergen beta-lactoglobulin. J Agric Food Chem. 52(5): 1398-1403.
Enomoto A, Konishi M, Hachimura S, Kaminogawa S.1993. Milk whey protein fed as a constituent of the diet induced both oral tolerance and a systemic humoral response, while heat-denatured whey protein induced only oral tolerance. Clin Immunol Immunopathol. 66(2): 136-142.
Enomoto A, Shon DH, Aoki Y, Yamauchi K, Kaminogawa S. 1990. Antibodies raised against peptide fragments of bovine as1-casein cross react with the intact protein only when the peptides contain both B and T cell determinants. Mol Immunol. 27:581–586.
Ermel RW, Kock M, Griffey SM, Reinhart GA, Frick OL.1997.The atopic dog: a model for food allergy. Lab Anim Sci. 47 (1): 40-49.
Exl BM, Fritsche R. 2001. Cow's milk protein allergy and possible means for its prevention. Nutrition. 17 (7-8): 642-651.
Fogolari F, Ragona L, Zetta L, Romagnoli S, C. G. de Kruif, Molinari H. 1998. Monomeric bovineβ-lactoglobulin adopts aβ-barrel fold at pH2. FEBS Lett. 436:149–154.
Fox and P. McSweeney, eds. Kluwer, Amsterdam, The Netherlands. Flower DR, North ACT, and Sansom CE. 2000. The lipocalin protein family—structural and sequence overview. Biochim. Biophys. Acta 1482:9–24.
Fritsche R, Adel-Patient K, Bernard H, Martin-Paschoud C, Schwarz C, Ah-Leung S, Wal JM. 2005. IgE-mediated rat mast cell triggering with tryptic and synthetic peptides of bovine beta-lactoglobulin. Int Arch Allergy Immunol. 138(4): 291-297.
Frossard CP, Hauser C, Eigenmann PA. 2001. Oral carrageenan induces antigen-dependent oral tolerance: prevention of anaphylaxis and induction of lymphocyte anergy in a murine model of food allergy. Pediatr Res. 49 (3): 417-422.
Frossard CP, Hauser C, Eigenmann PA. 2004a. Antigen-specific secretory IgA antibodies in the gut are decreased in a mouse model of food allergy. J Allergy Clin Immunol. 114 (2): 377-382.
Frossard CP, Tropia L, Hauser C, Eigenmann PA. 2004b. Lymphocytes in Peyer patches regulate clinical tolerance in a murine model of food allergy. J Allergy Clin Immunol. 113 (5): 958-964.
García-Ara C, Boyano-Martínez T, Díaz-Pena JM, Martín-Mu?oz F, Reche-Frutos M, Martín-Esteban M. 2001. Specific IgE levels in the diagnosis of immediate hypersensitivity to cow’s milk protein in the infant. J Allergy Clin Immunol. 107 (1):185-190.
Gaucheron Y, LeGraet K, Raulot, Piot M. 1997. Physicochemical characterization of iron-supplemented skim milk. International Dairy Journal. 7:141–148.
Gjesing B, Osterballe O, Schwartz B, Wahn U, Loewenstein H. 1986. Allergen-specific IgE antibodies against antigenic components in cow milk and milk substitutes. Allergy. 41 (1):51–56.
Goldman AS, Anderson DW, Sellers WA, Saperstein S, Kniker WT, Halpern ST. 1963. Milk allergy I Oral challenge with milk and isolated milk proteins in allergic children. Pediatrics. 32: 425–443.
Hambling SG, McAlpine AS, Sawyer L. 1992.β-Lactoglobulin in Advanced Dairy Chemistry-I: Proteins. P. F. Fox, ed. 140–191.
Hamosh M. 1996. Digestion in the newborn. Clin Perinatol. 23:191–209.
Harris BL. 1997. Selection to increaseβ-lactoglobulin B variant in New Zealand dairy cattle. in Milk Protein Polymorphism. J. P. Hill and M. Boland, eds. International Dairy. 467–473.
Havea, PH. Singh, and LK Creamer. 2001. Characterization of heat-induced aggregates of β-lactoglobulin,α-lactalbumin, and bovine serum albumin in a whey protein concentrate environment. J. Dairy Res. 68:483–497.
Hefle S L, Taylor S L .2004. Food allergy and the food industry Curr. Allergy Asthma Rep. 4:55–59.
Heine RG, Elsayed S, Hosking CS, Hill DJ. 2002. Cow’s milk allergy in infancy. Curr Opin Allergy Clin Immunol. 2(3):217-225.
Helm RM, Furuta GT, Stanley JS, Ye J, Cockrell G, Connaughton C, Simpson P, Bannon GA, Burks AW. 2002. A neonatal swine model for peanut allergy. J Allergy Clin Immunol.109(1): 136-142.
Herz U, Joachim R, Ahrens B, Scheffold A, Radbruch A , Renz H. 2001. Allergic sensitization and allergen exposure during pregnancy favor the development of atopy in the neonate. Int Arch Allergy Immunol. 124(1-3): 193-6.
Hill, JP, M. Boland and AF Smith. 1997. The effect ofβ-lactoglobulin variants on milk powder manufacture and properties. Pages 372–394 in Milk Protein Polymorphism. J. P. Hill and M. Boland, ed. International Dairy Federation, Brussels, Belgium.
H?st A, Halken S. 1990. A prospective study of cow milk allergy in Danish infants during the first 3 years of life. Clinical course in relation to clinical and immunological type of hypersensitivity reaction. Allergy. 45(8):587-596.
H?st A, Husby S, Osterballe O. 1988. A prospective study of cow’s milk allergy in exclusively breast-fed infants. Incidence, pathogenetic role of early inadvertent exposure to cow′s milk formula, and characterization of bovine milk protein in human milk. Acta Paediatr Scand; 77(5):663-70.
H?st A. 1994. Cow’s milk protein allergy and intolerance in infancy. Some clinical, epidemiological and immunological aspects. Pediatr Allergy Immunol. 5(5 Suppl):1-36.
H?st A. 2002. Frequency of cow’s milk allergy in childhood. Ann Allergy Asthma Immunol. 89 (6 Suppl I):33-37.
Iametti S, De Gregori B, Vecchio G, Bonomi F. 1996. Modifications occur at different structural levels during the heat denaturation of beta-lactoglobulin. Eur J Biochem .237(1): 106-112.
Ignatowski TA, Bidlack JM. 1999. Differential kappa-opioid receptor expression on mouse lymphocytes at varying stages of maturation and on mouse macrophages after selective elicitation. The Journal of Pharmacology and Experimental Therapeutics. 290: 863-870.
Imaizumi A, Kawakami T, Murakami F, Soma Y, Mizoguchi M. 2003. Effective treatment of pruritus in atopic dermatitis using H1 antihistamines (second-generation antihistamines): changes in blood histamine and tryptase levels. Journal of Dermatological Science. 33 (1):23-29.
Inoue R, Matsushita S, Kaneko H, Shinoda S, Sakaguchi H, Nishimura Y, Kondo N.2001. Identification of beta-lactoglobulin-derived peptides and class II HLA molecules recognized by T cells from patients with milk allergy. Clin Exp Allergy. 31 (7): 1126-1134.
Ishizaka T, Tomioka H, Ishizaka K. 1971. Degranulation of human basophil leukocytes by anti-g E antibody. J Immunol.106:705-710.
Jakobsson I, Lothe L, Borschel MW. 2000. Effectiveness of casein hydrolysate feedings in infants with colic. Acta Paediatr. 89 (1):18-21.
Jakobsson O, Lindberg T. 1979. A prospective study of cow’s milk protein intolerance in Swedish infants. Acta Paediatr Scand. 68 (6):853-859.
Jameson G B, Adams JJ, Creamer LK. 2002. Flexibility, functionality and hydrophobicity of bovineβ-lactoglobulins. Int Dairy J. 12:319–329.
Jarvinen KM, Beyer K, Vila L, Chatchatee P, Busse PJ, Sampson HA. 2002. B-cell epitopes as a screening instrument for persistent cow’s milk allergy. J Allergy Clin Immunol. 110 (2): 293–297.
Jarvinen KM, Chatchatee P, Bardina L, Beyer K, Sampson HA. 2001. IgE and IgG binding epitopes on alpha-lactalbumin and betalactoglobulin in cow’s milk allergy. Int Arch Allergy Immunol. 126 (2); 111–118.
Ju HR, Okumiya M, Nishizono S, Ki M, Sugano M, Imaizumi K.1997. Increase in degranulation of mucosal mast cells in rats sensitized with milk whey protein hydrolysates compared with native proteins. Food Chem Toxicol. 35(7): 663-668.
Karamanova L, Fukal L, Kodicek M, Rauch P, Mills E, Morgan M. 2003. Effect of Heat Treatment on the Detection of Intact Bovineβ-Lactoglobulins by LC Mass Spectrometry. Food Agric Immunol. 15:77–91
Karine APC. Creminon H, Bernard G, Clement L, Negronil Y, Frobert J, Grassi, Wal JM. 2000. Evaluation of a high IgE-responder mouse model of allergy to bovineβ- lactoglobulin: development of sandwich immunoassays for total and allergen-specific IgE, IgG1 and IgG2a in β-lg-sensitized mice. Journal of Immunological Methods. 235:21–32.
Kato C, Sato K, Eishi Y, Nakamura K. 1999. The influence of initial exposure timing to beta-lactoglobulin on oral tolerance induction. J Allergy Clin Immunol. 104(4 Pt 1): 870-878.
Kimura K, Adachi M, Kubo K, Ikemoto Y.1999. The basal plasma histamine level andeosinophil count in allergic and non-allergic patients. Fukuoka Igaku Zasshi. 90 (12): 457-463.
Kinsella JE, and D M Whitehead. 1989. Proteins in whey: Chemical, physical and functional properties. Adv Food Nutr Res. 33:343–438.
Kitabatake N, Kinekawa Y. 1998. Digestibility of Bovine Milk Whey Protein and β-Lactoglobulin in Vitro and in Vivo. J Agric Food Chem. 46 (12): 4917-4923.
Kitagawa S, Zhang S, Harari Y, Castro GA. 1995. Relative allergenicity of cow's milk and cow's milk-based formulas in an animal model. Am J Med Sci. 310 (5): 183-187.
Klemola T, Vanto T, Juntunen-Backman K, Kalimo K, Korpela R, Varjonen E. 2002. Allergy to soy formula and to extensively hydrolyzed whey formula in infants with cow’s milk allergy: a prospective, randomized study with a follow-up to the age of 2 years. J Pediatr. 140 (2):219-224.
Knippels LM, Houben GF, Spanhaak S, Penninks AH. 1999a. An oral sensitization model in Brown Norway rats to screen for potential allergenicity of food proteins. Methods. 19 (1): 78-82.
Knippels LM, Penninks AH, Spanhaak S, Houben GF. 1998b. Oral sensitization to food proteins: a Brown Norway rat model. Clin Exp Allergy. 28(3): 368-375.
Knippels LM, Penninks AH, van Meeteren M, Houben GF. 1999c. Humoral and cellular immune responses in different rat strains on oral exposure to ovalbumin. Food Chem Toxicol. 37 (8): 881-888.
Knippels LMJ, Penninks AH, Smit JJ, Houben GF. 1999d. Immune-Mediated Effects upon Oral Challenge of Ovalbumin-Sensitized Brown Norway Rats: Further Characterization of a Rat Food Allergy Model. Toxicol Appl Pharmaco.l 156 (3): 161-169.
Kobayashi K, Hirano A, Ohta A, Yoshida T, Takahashi K, Hattori M. 2001. Reduced immunogenicity of beta-lactoglobulin by conjugation with carboxymethyl dextran differing in molecular weight. Journal of Agricultural and Food Chemistry. 49: 823~831.
Kobayashi T, Ikeguchi M, Sugai S. 2000. Molten globule structure of equineβ-lactoglobulin probed by hydrogen exchange. J Mol Biol. 299:757–770.
Koldovsky O. 1984. J Am Coll Nutr. 3:131–138
Koshibu T. 1994. Measurement of plasma histamine, urinary N-methylhistamine and peripheral eosinophil counts in food provocation tests in infants and children with atopic dermatitis. Arerugi. 43 (7):787-795.
Kraulis PJ. 1991. MOLSCRIPT—A program to produce both detailed and schematic plots of protein structures. J Appl Cryst. 24:946–950.
Kurisaki J, Nakamura S, Kaminogawa S, Yamauchi K.1982. The antigenic properties of β-lactoglobulins examined with mouse IgE antibody. Agric Biol Chem. 4: 2069-2075.
Kuwata K, M Hoshino, S Era, C A Batt, Y Goto. 1998. Theα-βtransition ofβ-lactoglobulin as evidenced by heteronuclear NMR. J. Mol. Biol. 283:731–739.
Lara V.F, M. Olivares, and J. Xaus. 2005. The balance between caseins and whey proteins in cow’s milk determines its allergenicity. J. Dairy Sci. 88:1654-1660.
Lee YH. 1992. Food-processing approaches to altering allergenic potential of milk-basedformula J Pediatr. 121:47–50.
Li XM, Schofied BH, Huang CK, Kleiner GI, Sampson HA. 1999. A murine model of IgE-mediated cow’s milk hypersensitivity. J Allergy Clin Immunol. 103:206-214.
Lombardi G, Miglio G, Dianzani C, Mesturini R, Varsaldi F, Chiocchetti A, et al. 2004. Glutamate modulation of human lymphocyte growth: In vitro studies, Biochemical and Biophysical Research Communications. 318:496-502.
Lyster RLJ. 1972. Reviews of the progress of dairy science. Section C. Chemistry of milk proteins. J Dairy Res. 39:279–318.
Mahmud R, Matn MA, Otani H. 2004. Mitogenic effect of bovine b-lactoglobulin and its proteolytic digests on mouse spleen resting cells. Pakistan Journal of Biological Sciences. 7(12): 2045-2050.
Mailliart P, Ribadeau-Dumas B. 1988. Preparation of B-Lactoglobulin And B-Lactoglobulin Free Proteins From Whey Retentate By NaCl Salting Out At Low pH. Journal of Food Science.53: 743-745.
M?kinen-Kiljunen S, Palosuo T. 1992. A sensitive enzyme-linked immunosorbent assay for determination of bovine beta-lactoglobulin in infant feeding formulas and in human milk. Allergy. 47 (4 Pt 2):347-352.
Mansouri A, Gueant JL, Capiaumont J, Pelosi P, Nabet P, Haertle T. 1998. Plasma membrane receptor for beta-lactoglobulin and retinol-binding protein in murine hybridomas. Biofactors. 7(4): 287-298.
Mansouri A, Haertle T, Gerard A, Gerard H, Gueant JL. 1997. Retinol free and retinol complexed beta-lactoglobulin binding sites in bovine germ cells. Biochim Biophys Acta. 1357(1): 107-114.
Martelli A, De Chiara A, Corvo M, Restani P, Fiocchi A. 2002. Beef allergy in children with cow’s milk allergy; cow’s milk allergy in children with beef allergy. Ann Allergy Asthma Immunol. 89(6 Suppl 1):38-43.
Martin TR, Galli SJ, Katona IM, Drazen JM. 1989. Role of mast cells in anaphylaxis. Evidence for the importance of mast cells in the cardiopulmonary alterations and death induced by anti-IgE in mice. J Clin Invest. 83:1375-1383.
Maynard F, Jost R, Wal JM. 1997. Human IgE binding capacity of tryptic peptides from bovine alpha–lactalbumin. Int Arch Allergy Immunol. 113:478–488.
McKenzie HA, Sawyer WH. 1967. Effect of pH onβ-lactoglobulins. Nature 214:1101–1104.
McLain BI, Cameron DJ, Barnes GL. 1994. Is cow’s milk protein intolerance a cause of gastro-oesophageal reflux in infancy? J Paeditr Child Health. 30(4):316-318.
Mercier A, Gauthier SF, Fliss I. 2004. Immunomodulating effects of whey proteins and their enzymatic digests. International Dairy Journal. 14:175-183.
Miller K, Laugee J, Meredith C.1998. The monitoring of the effects of food components on immunoreactivity in experimental animals. Allergy. 53 (46 Suppl): 35-37.
Miller K, Meredith C, Selo I, Wal JM. 1999. Allergy to bovine beta-lactoglobulin: specificity of immunoglobulin E generated in the Brown Norway rat to tryptic and synthetic peptides. Clin Exp Allergy. 29 (12): 1696-1704.
Miyauchi H, Kaino A, Shinoda I, Fukuwatari Y, Hayasawa H. 1997. Immunomodulatory effect of bovine lactoferrin pepsin hydrolysate on murine splenocytes and Peyer’s patch cells. Journal of Dairy Science. 80 (10):2330-2339.
Mizuno S, Nishimura S, Matsuura K, Gotou T, Yamamoto N. 2004. Release of short and proline-rich antihypertensive peptides from casein hydrolysate with an Aspergillus oryzae protease. J Dairy Sci. 87:3183–3188.
Monnai M, Horimoto Y, Otani H. 1998. Immunomodificatory effect of dietary bovine kappa-caseinoglycopeptide on serum antibody levels and proliferative responses of lymphocytes in mice. Milchwissenshaft. 53:129-132.
Muller-Renaud S, Dupont D, Dulieu P. 2004. Quantification of beta-casein in milk and cheese using an optical immunosensor. J Agric Food Chem. 52:659–664.
Murosaki S, Yamamoto Y, Ito K, Inokuchi T, Kusaka H, Ikeda H, Yoshikai Y. 1998.
Heat-killed Lactobacillus plantarum L-137 suppresses naturally fed antigen-specific IgE production by stimulation of IL-12 production in mice. J Allergy Clin Immunol. 102(1): 57-64.
Natale M, Bisson C, Monti G, Peltran A, Garoffo LP, Valentini S, Fabris C, Bertino E, Coscia A, Conti A. 2004. Cow’s milk allergens identification by two-dimensional immunoblotting and mass spectrometry. Mol Nutr Food Res. 48 (5):363–369.
Negroni L, Bernard H, Clement G, Chatel JM, Brune P, Frobert Y, Wal JM, Grassi J. 1998.
Two-site enzyme immunometric assays for determination of native and denatured beta-lactoglobulin. J Immunol Methods. 220: 25-37.
Nielsen BR, Poulsen OM, Hau J.1989. Reagin production in mice: effect of subcutaneous and oral sensitization with untreated bovine milk and homogenized bovine milk. In Vivo. 3(4): 271-274.
Oldfield DJ, Singh H, Taylor MW. 2005. Kinetics of heat-induced whey protein denaturation and aggregation in skim milks with adjusted whey protein concentration. J Dairy Res. 72(3): 369-378.
Oliveira KM, Valente-Mesquita VL, Botelho MM, Sawyer L, Ferreira ST, Polikarpov I. 2001. Crystal structures of bovine beta-lactoglobulin in the orthorhombic space group C222(1). Structural differences between genetic variants A and B and features of the Tanford transition. Eur J Biochem. 268 (2): 477-483.
Otani H, Uchio T, Tokita F. 1985. Antigenic reactivities of chemically modified β-lactoglobulins with antiserum to bovineβ-lactoglobulins. Agric Biol Chem. 49: 2531-2536.
Ouwehand AC, Salminen SJ, Skurnik M, Conway PL. 1997. Inhibition of Pathogen Adhesion by Beta-Lactoglobulin. Int Dairy J. 7(11): 685-692.
Paajanen L, Tuure T, Poussa T, Korpela R. 2003. No difference in symptoms during challenges with homogenized and unhomogenized cow's milk in subjects with subjective hypersensitivity tohomogenized milk. J Dairy Res. 70 (2): 175-179.
Paajanen L, Tuure T, Vaarala O, Korpela R. 2005. Homogenization of milk has no effect on milk-specific antibodies in healthy adults. Milchwissenschaft. 60 (3): 239-241.
Papiz MZ, Sawyer L, Eliopoulos EE, North AC, Findlay JB, Sivaprasadarao R, Jones TA, Newcomer ME, Kraulis PJ. 1986. The structure of beta-lactoglobulin and its similarity to plasma retinol-binding protein. Nature 324 (6095): 383-385.
Pecquet S, Bovetto L, Maynard F, Fritsche R. 2000. Peptides obtained by tryptic hydrolysis of bovine beta-lactoglobulin induce specific oral tolerance in mice. J Allergy Clin Immunol. 105(3): 514-521.
Penninks AH, Knippels LM. 2001. Determination of protein allergenicity: studies in rats. Toxicol Lett. 120(1-3): 171-180.
Perez MD, Sanchez L, Aranda P, Ena J, Oria R, Calvo M. 1992. Effect of beta-lactoglobulin on the activity of pregastric lipase. A possible role for this protein in ruminant milk. Biochim Biophys Acta. 1123(2): 151-155.
Piaial M, Antoinel JM, Guardia JAM. 2003. Assessment of the Benefits of Live Yogurt: Methods and Markers for in vivo Studies of the Physiological Effects of Yogurt Cultures. Microbial Ecology in Health and Disease. 15: 79-87
Pihlanto-Leppala A, Paakkari I, Rinta-Koski M, Antila P. 1997. Bioactive peptide derived from in vitro proteolysis of bovine beta-lactoglobulin and its effect on smooth muscle. J Dairy Res. 64(1): 149-155.
Pihlanto-Leppala A. 2000. Bioactive peptides derived from bovine whey proteins: opioid and ace-inhibitory peptides. Trends Food Sci Tech. 11(9-10): 347-356.
Plebani A, Restani P, Naselli A, Galli CL, Meini A, Cavagni G, Ugazio AG, Poiesi C. 1997.
Monoclonal and polyclonal antibodies against casein components of cow milk for evaluation of residual antigenic activity in 'hypoallergenic' infant formulas. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology. 27(8):949-956.
Poulsen OM, Hau J, Kollerup J. 1987. Effect of homogenization and pasteurization on the allergenicity of bovine milk analysed by a murine anaphylactic shock model. Clin Allergy. 17 (5): 449-458.
Poulsen OM, Nielsen BR, Basse A, Hau J.1990. Comparison of intestinal anaphylactic reactions in sensitized mice challenged with untreated bovine milk and homogenized bovine milk. Allergy. 45 (5): 321-326.
Puyol P, Perez MD, Sanchez L, Ena JM, Calvo M. 1995. Uptake and passage of beta-lactoglobulin, palmitic acid and retinol across the Caco-2 monolayer. Biochim Biophys Acta. 1236(1): 149-154.
Qi XL, Brownlow S, Holt C, Sellers P. 1995. Thermal denaturation of beta-lactoglobulin: effect of protein concentration at pH 6.75 and 8.05. Biochim Biophys Acta. 1248 (1): 43-49.
Qi XL, Holt C, McNulty D, Clarke DT, Brownlow S, Jones GR. 1997. Effect of temperatureon the secondary structure of beta-lactoglobulin at pH 6.7, as determined by CD and IR spectroscopy: a test of the molten globule hypothesis. Biochem J. 324 (Pt 1): 341-346.
Qin BY, Bewley MC, Creamer LK, Baker HM, Baker EN, Jameson GB. 1998. Structural basis of the Tanford transition of bovine beta-lactoglobulin. Biochemistry. 37(40): 14014-14023.
Reddy I, Kella N. Kinsella J. 1988. Structural and conformational basis of the resistance of beta-lactoglobulin to peptic and chymotryptic digestion. J Agric Food Chem.
Restani P, Gaiaschi A, Plebani A, Beretta B, Cavagni G, Fiocchi A. 1999. Cross-reactivity between milk proteins from different animal species. Clin Exp Allergy. 29(7):997-1004.
Restani P, Plebani A, Velona T, Cavagni G, Ugazio AG, Poiesi C, Muraro A, Galli CL. 1996.
Use of immunoblotting and monoclonal antibodies to evaluate the residual antigenic activity of milk protein hydrolysed formulae. Clin Exp Allergy 26:1182–1187.
Rico AI, Girones N, Fresno M, Alonso C, Requena JM. 2002. The heat shock proteins, Hsp70 and Hsp83, of Leishmania infantum are mitogens for mouse B cells. Cell Stress & Chaperones. 7: 339-346.
Ring J, Senter T, Cornell RC, Arroyave CM, Tan EM. 979. Plasma complement and histamine changes in atopic dermatitis. British Journal of Dermatology. 100 (5):521-530.
Roefs SP, De Kruif KG. 1994. A model for the denaturation and aggregation of beta-lactoglobulin. Eur J Biochem. 226(3): 883-889.
Rowland SJ. 1938. The Protein Distribution In Normal And Abnormal Milk. Journal of Dairy Research. 9:47-57.
Rozenfeld P, Docena GH, A?ón MC, Fossati CA. 2002. Detection and identification of a soy protein component that cross-reacts with caseins from cow’s milk. Clin Exp Immunol. 130(1):49-58.
Saarinen KM, Juntunen-Backman K, Jarvenpaa AL, Kuitunen P, Lope L, Renlund M, Siivola M, Savilahti E. 1999. Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants. J Allergy Clin Immunol. 104 (2 Pt 1): 457-461.
Saarinen KM, Juntunen-Backman K, J?venp?? AL, Klemetti P, Kuitunen P, Lope L. 2000. Breast-feeding and the development of cow′s milk protein allergy. Adv Exp Med Biol. 478:121-30.
Sakaguchi H, Inoue R, Kaneko H, Watanabe M, Suzuki K, Kato Z, Matsushita S, Kondo N. 2002. Interaction among human leucocyte antigen-peptide-T cell receptor complexes in cow's milk allergy: the significance of human leucocyte antigen and T cell receptor-complementarity determining region 3 loops. Clin Exp Allergy. 32 (5): 762-770.
Sakurai K, Goto Y. 2002. Manipulating monomer-dimer equilibrium of bovineβ-lactoglobulin by amino acid substitution. J. Biol. Chem. 277: 25735–25740.
Salvatore S, Vandenplas Y. 2002. Gastroesophageal reflux and cow milk allergy: is there a link? Pediatrics. 110 (5):972-984.
Sampson HA, Jolie PL. 1984. Increased plasma histamine concentrations after food challenges in children with atopic dermatitis. New England Journal of Medicine. 311(6): 372-376.
Sampson HA. 1999. Food allergy. Part 1: immunopathogenesis and clinical disorders. J Allergy Clin Immunol. 103(5 Pt 1): 717-728.
Sawyer L, Kontopidis G. 2000. The core lipocalin, bovine beta-lactoglobulin. Biochim Biophys Acta. 1482 (1-2): 136-148.
Sawyer L. 2003.β-Lactoglobulin. Pages 319–386 in Advanced Dairy Chemistry I, 3rd ed. P. F. Sawyer L. 2003.β-lactoglobulin. In: P. F. Fox and P. L. H. McSweeney (eds) Advanced dairy chemistry, Volume 1, 3rd Edn, Kluwer Academic/Plenum Publishers, 319-386.
Selo I, Clement G, Bernard H, Chatel J, Creminon C, Peltre G, Wal J. 1999. Allergy to bovine beta-lactoglobulin: specificity of human IgE to tryptic peptides. Clin Exp Allergy 29 (8): 1055 -1063.
Selo I, Negroni L, Creminon C, Yvon M, Peltre G, Wal JM. 1998. Allergy to bovine beta -lactoglobulin: specificity of human IgE using cyanogen bromide-derived peptides. Int Arch Allergy Immunol. 117 (1): 20-28.
Song CY, Chen WL, Yang MC, Huang JP, Mao SJ. 2005. Epitope mapping of a monoclonal antibody specific to bovine dry milk: involvement of residues 66-76 of strand D in thermal denatured beta-lactoglobulin. J Biol Chem. 280 (5): 3574-3582.
Takagi K, Teshima R, Okunuki H & Sawada J.2003. Comparative study of in vitro digestibility of food proteins and effect of preheating on the digestion. Biol Pharm Bulletin. 26(7): 969-973.
Tanford C, Bunville LG, Nozak Y i. 1959. The reversible transformation ofβ-lactoglobulin at pH 7.5. J Am Chem Soc. 81:4032–4036.
Tanford C, Taggart V. 1961. Ionization-linked Changes in Protein Conformation. II. The N–R Transition inβ-Lactoglobulin. J Amer Chem Soc. 83: 1634-1638.
Terpend K, Blaton MA, Candalh C, Wal JM, Pochart P, Heyman M. 1999. Intestinal barrier function and cow's milk sensitization in guinea pigs fed milk or fermented milk. J Pediatr Gastroenterol Nutr. 28(2): 191-198.
Tilley, J. M. A. 1960. The chemical and physical properties of bovineβ-lactoglobulin. Dairy Sci. Abstr. 22:111–125.
Totsuka M, Ametani A, Kaminogawa S. 1997. Fine mapping of T-cell determinants of bovine beta-lactoglobulin. Cytotechnology. 25(1-3): 101-113.
Tsuji NM, Kurisaki J, Mizumachi K, Kaminogawa S.1993. Localization of T-cell determinants on bovine beta-lactoglobulin. Immunol Lett. 37(2-3): 215-221.
Uhrinova S, Smith MH, Jameson GB, Uhrin D, Sawyer L, Barlow PN. 2000. Structural changes accompanying pH induced dissociation of theβ-lactoglobulin dimmer. Biochemistry 39: 3565–3574.
Valkonen KH, Rytk?nen J, Karttunen TJ, Kokkonen J, Alatossava T. 2002. Tools for analyzing immunological responses to betalactoglobulin in animal models: Significance of heat denaturation. In: T. Alatossava (ed) Immunological and Biochemical Tools for Analysis of Dairy Starters, Processes, and Products. Trivandrum, Kerala, India, Research Signpost, 125-137.
Villamiel M, Lopez-Fandino R, Corzo N, Olano A. 1997. Denaturation of beta-lactoglobulin and native enzymes in the plate exchanger and holding tube section during continuous flow pasteurization of milk. Food Chem. 58(1-2): 49-52.
von der Weid T, Bulliard C, Fritsche R.2001. Suppression of specific and bystander IgE responses in a mouse model of oral sensitization to beta-lactoglobulin. Int Arch Allergy Immunol. 125(4): 307-15.
Wong KF, Middleton N, Montgomery M, Dey M, Carr RI. 1998. Immunostimulation of murine spleen cells by materials associated with bovine milk protein fractions. Journal of Dairy Science. 81:1825–1832.
Wroblewska B, Karamc M, Amarowicz R. 2004. Immuorective properties of peptide fractions of cow whey milk proteins after enzymatic hydrolysis.International jouranl of food science and technology. 39:839-850.
Wróblewska BL, J?drychowski. 2005. Influence of Enzymatic Cow Milk Hydrolysates on IgA and IgG Response of Balb/c Mice Organism. Czech J Food Sci. 23:51-63.
Yamauchi R, Usui H, Yunden J, Takenaka Y, Tani F, Yoshikawa M. 2003. Characterization of beta-lactotensin, a bioactive peptide derived from bovine beta-lactoglobulin, as a neurotensin agonist. Biosci Biotechnol Biochem. 67(4): 940-943.
李欣,陈红兵.2005.过敏原在食品加工中的变化.食品工业. 1:50-52.
赵新淮.1994.蛋白质水解物水解度的测定.食品科学.11:65～67
Adel-Patient K, Creminon C, Bernard H, Clement G, Negroni L, Frobert Y, Grassi J, Wal JM, Chatel JM. 2000. Evaluation of a high IgE-responder mouse model of allergy to bovine beta- lactoglobulin (β-lg): development of sandwich immunoassays for total and allergen-specific IgE, IgG1 and IgG2a inβ-lg sensitized mice. J Immunol Methods. 235(1-2): 21-32.
Andre F, Andre C, Colin L, Cacaraci F, Cavagna S. 1994. Role of new allergens and of allergens consumption in the increased incidence of food sensitizations in France. Toxicology. 93(1): 77-83.
Anema A, Ritmeijer K. 2005. Treating HIV/AIDS and leishmaniasis coinfection in Ethiopia. CMAJ. 172(11):1434-1435.
Anguita G, Martin R, Garcia T, Morales P, Haza AI, Gonzalez I, Sanz B, Hernandez PE. 1997.
A competitive enzyme-linked immunosorbent assay for detection of bovine milk in ovine and caprine milk and cheese using a monoclonal antibody against bovine beta-casein. J Food Prot. 60:64–66.
Anveden-Hertzberg L, Finkel Y, Sandstedt B, Karpe B. 1996. Proctocolitis in exclusively breast-fed infants. Eur J Pediatr. 155(6):464-467.
Arshad SH, Tariq SM, Matthews S, Hakim E. 2001. Sensitization to common allergens and its association with allergic disorders at age 4 years: a whole population birth cohort study. Pediatrics. 108(2):E33.
Asselin J, Hebert J, Amiot J. 1989. Effects of in vitro proteolysis on the allergenicity of major whey proteins,J Food Sci. 54:1037–1039.
Astwood JD, Leach JN, Fuchs RL. 1996. Stability of food allergens to digestion in vitro. Nat Biotechnol. 14(10): 1269-1273.
Baehler P, Chad Z, Gurbindo C, Bonin AP, Bouthillier L, Seidman EG. 1996. Distinct patterns of cow’s milk allergy in infancy defined by prolonged, two-stage double blind, placebo-controlled food challenges. Clin Exp Allergy. 26(3):254-61.
Baumgarth N. 2000. A two-phase model of B-cell activation. Immunological Reviews. 176: 171–180.
Beavis AJ, Pennline KJ. 1994. Simultaneous measurement of fivecell surface antigens by five-colour immunofluorescence. Cytometry. 15:371-376.
Belloque J, and Smith GM. 1998. Thermal denaturation ofβ-lactoglobulin. A 1H NMR study. J Agric Food Chem. 46:1805–1813.
Bernard H, Creminon C, Yvon M, Wal JM. 1998. Specificity of the human IgE response to the different purified caseins in allergy to cow’s milk proteins. Int Arch Allergy Immunol. 115 (3): 235–244.
Bertrand-Harb C, Baday A, Dalgalarrondo M, Chobert JM, Haertle T.2002. Nahrung 46:283–289.
Bevilacqua C, Martin P, Candalh C, Fauquant J, Piot M, Roucayrol AM, Pilla F, Heyman M. 2001. Goat’s milk of defective alpha (s1)-casein genotype decreases intestinal and systemic sensitization to beta-lactoglobulin in guinea pigs. J Dairy Res. 68 (2):217–227.
Black CL, Reynolds EC.1998. An ELISA for a multi-phosphorylated peptide, as1-casein (59-79). J Immunol Methods. 214:63–71.
Blais BW, Gaudreault M, Phillippe LM. 2003 Multiplex enzyme immunoassay system for the simultaneous detection of multiple allergens in foods. Food Control. 14:43–47.
Blaise F, GagnéM, Salazar S, Salazar S, Trottier, Hansen PD. 2003. Expmentally-induced feminisation of freshwater mussels after long-term exposure to a municipal effluent, Fresenius Environ Bull. 12:865–870.
Bock SA, Sampson HA, Atkins FM, Zeiger RS, Lehrer S, Sachs M. 1988. Doubleblind placebo-controlled food challenge (DBPCFC) as an office procedure: a manual. J Allergy Clin Immunol. 82(6):986-997.
Bonomi F, Fiocchi A, Frokiaer H, Gaiaschi A, Iametti S, Poiesi C, Rasmussen P, Restani P, Rovere P. 2003. Reduction of immunoreactivity of bovine beta-lactoglobulin upon combined physical and proteolytic treatment,J Dairy Res. 70:51–59.
Brix S, Bovetto L, Fritsche R, Barkholt V, Frokiaer H. 2003. Immunostimulatory potential of beta-lactoglobulin preparations: Effects caused by endotoxin contamination. Journal of Allergy and Clinical Immunology. 112(6): 1216–1222.
Brix S, Christensen HR, Barkholt V, Frokiaer H. 2005. Effect of Maternal Dietary Cow's Milk on the Immune Response to Beta-Lactoglobulin in the Offspring: A Four-Generation Study in Mice. Int Arch Allergy Immunol. 136(3): 250-257.
Brownlow S, Cabral JHM, Cooper R, Flower DR, Yewdall SJ, Polikarpov I, North ACT, Sawyer L. 1997. Bovineβ-lactoglobulin at 1.8 angstrom resolution—still an enigmatic lipocalin. Structure 5:481–495.
Burczynski FJ, Moran JB, Cai ZS, Forker EL.1990. Beta-lactoglobulin enhances the uptake of free palmitate by hepatocyte monolayers: the relative importance of diffusion and facilitated dissociation. Can J Physiol Pharmacol. 68(2): 201-216.
Busse PJ, Jarvinen KM, Vila L, Beyer K, Sampson HA. 2002. Identification of sequential IgE-binding epitopoes on bovine alpha (S2) casein in cow’s milk allergic patients. Int Arch Allergy Immunol. 129 (1): 93–96.
Canani RB, Ruotolo S, Auricchio L, Caldore M, Porcaro F, Manguso F. 2007. Diagnostic accuracy of the atopy patch test in children with food allergy-related gastrointestinal symptoms. Allergy. 62(7):738-43.
Cantani A, Lucenti P. 1997. Natural history of soy allergy and/or intolerance in children, and clinical use of soy-protein formulas. Pediatr Allergy Immunol. 8(2):59-74.
Casal HL, Kohler U, Mantsch HH.1988. Structural and conformational changes of beta- lactoglobulin B: an infrared spectroscopic study of the effect of pH and temperature. Biochim Biophys Acta. 957(1): 11-20.
Cavagni G, Plebani A, Restani P, Marini S, Gardenghi M, Poiesi C, Duse M, Ugazio AG. 1994.
Allergy to cow’s milk proteins in childhood: the author’s personal experience and new diagnostic and therapeutic proposals. Pediatr Med Chir. 16 (5):413–419.
Cocco RR, Jarvinen KM, Sampson HA, Beyer K. 2003. Mutational analysis of major sequential IgE-binding epitopes in alphas1-casein, a major cow’s milk allergen. J Allergy Clin Immunol. 112 (2):433–437.
Creamer LK, Bienvenue A, Nilsson H, Paulsson M, van Wanroij M, Lowe EK, Anema SG, Boland MJ, Jimenez-Flores R. 2004. Heat-Induced Redistribution of Disulfide Bonds in Milk Proteins. 1. Bovine beta-Lactoglobulin. J Agric Food Chem. 52(25): 7660-7668.
Cross ML, Gill HS. 1999. Modulation of immune function by a modified bovine whey protein concentrate, Immunology and Cell Biology. 77: 345-350.
Cross ML, Stevenson LM, Gill HS. 2001. Anti-allergy properties of fermented foods: an important immunoregulatory mechanism of lactic acid bacteria. International Immuno pharmacology. 1: 891-901.
Dahlgren UI, Wold AE, Hanson LA, Midtvedt T. 1991. Secretory antibody response against bacterial antigens and food proteins. Immunol Res. 10(3-4): 437-440.
Davis PJ, Williams SC. 1998. Protein modification by thermal processing. Allergy 53(46 Suppl): 102-105.
Dearman RJ, Caddick H, Stone S, Basketter DA, Kimber I. 2001. Characterization of antibody responses induced in rodents by exposure to food proteins: influence of route of exposure. Toxicology. 167(3): 217-231.
Dearman RJ, Kimber I. 2001. Determination of protein allergenicity: studies in mice. Toxicol Lett. 120(1-3): 181-186.
del Val G, Yee BC, Lozano RM, Buchanan BB, Ermel RW, Lee YM, Frick OL .1999.
Thioredoxin treatment increases digestibility and lowers allergenicity of milk. J Allergy Clin Immunol. 103(4): 690-697.
Diane Saint-Sauveura, Sylvie F. Gauthiera, Yvan Boutinb, Alicia Montonia. 2008.
Immunomodulating properties of a whey protein isolate, its enzymatic digest and peptide fractions. International Dairy Journal. 18: 260-270.
Docena G, Rozenfeld P, Fernándea R, Fassati CA.2002. Evaluation of the residual antigenicityand allergenicity of cow’s milk substitutes by in vitro tests. Allergy. 57(2): 83-91.
Docena GH, Fernandez R, Chirdo FG, Fossati CA. 1996. Identification of casein as the major allergenic and antigenic protein of cow’s milk. Allergy. 51 (6):412–416.
Dupont D, Rolet-Repecaud O, Muller-Renaud S. 2004. Determination of the heattreatment undergone by milk by following the denaturation ofα-lactalbumin with a biosensor J Agric Food Chem. 52:677–681.
Ehn BM, Ekstrand B, Bengtsson U, Ahlstedt S.2004. Modification of IgE binding during heat processing of the cow's milk allergen beta-lactoglobulin. J Agric Food Chem. 52(5): 1398-1403.
Enomoto A, Konishi M, Hachimura S, Kaminogawa S.1993. Milk whey protein fed as a constituent of the diet induced both oral tolerance and a systemic humoral response, while heat-denatured whey protein induced only oral tolerance. Clin Immunol Immunopathol. 66(2): 136-142.
Enomoto A, Shon DH, Aoki Y, Yamauchi K, Kaminogawa S. 1990. Antibodies raised against peptide fragments of bovine as1-casein cross react with the intact protein only when the peptides contain both B and T cell determinants. Mol Immunol. 27:581–586.
Ermel RW, Kock M, Griffey SM, Reinhart GA, Frick OL.1997.The atopic dog: a model for food allergy. Lab Anim Sci. 47 (1): 40-49.
Exl BM, Fritsche R. 2001. Cow's milk protein allergy and possible means for its prevention. Nutrition. 17 (7-8): 642-651.
Fogolari F, Ragona L, Zetta L, Romagnoli S, C. G. de Kruif, Molinari H. 1998. Monomeric bovineβ-lactoglobulin adopts aβ-barrel fold at pH2. FEBS Lett. 436:149–154.
Fox and P. McSweeney, eds. Kluwer, Amsterdam, The Netherlands. Flower DR, North ACT, and Sansom CE. 2000. The lipocalin protein family—structural and sequence overview. Biochim. Biophys. Acta 1482:9–24.
Fritsche R, Adel-Patient K, Bernard H, Martin-Paschoud C, Schwarz C, Ah-Leung S, Wal JM. 2005. IgE-mediated rat mast cell triggering with tryptic and synthetic peptides of bovine beta-lactoglobulin. Int Arch Allergy Immunol. 138(4): 291-297.
Frossard CP, Hauser C, Eigenmann PA. 2001. Oral carrageenan induces antigen-dependent oral tolerance: prevention of anaphylaxis and induction of lymphocyte anergy in a murine model of food allergy. Pediatr Res. 49 (3): 417-422.
Frossard CP, Hauser C, Eigenmann PA. 2004a. Antigen-specific secretory IgA antibodies in the gut are decreased in a mouse model of food allergy. J Allergy Clin Immunol. 114 (2): 377-382.
Frossard CP, Tropia L, Hauser C, Eigenmann PA. 2004b. Lymphocytes in Peyer patches regulate clinical tolerance in a murine model of food allergy. J Allergy Clin Immunol. 113 (5): 958-964.
García-Ara C, Boyano-Martínez T, Díaz-Pena JM, Martín-Mu?oz F, Reche-Frutos M, Martín-Esteban M. 2001. Specific IgE levels in the diagnosis of immediate hypersensitivity to cow’s milk protein in the infant. J Allergy Clin Immunol. 107 (1):185-190.
Gaucheron Y, LeGraet K, Raulot, Piot M. 1997. Physicochemical characterization of iron-supplemented skim milk. International Dairy Journal. 7:141–148.
Gjesing B, Osterballe O, Schwartz B, Wahn U, Loewenstein H. 1986. Allergen-specific IgE antibodies against antigenic components in cow milk and milk substitutes. Allergy. 41 (1):51–56.
Goldman AS, Anderson DW, Sellers WA, Saperstein S, Kniker WT, Halpern ST. 1963. Milk allergy I Oral challenge with milk and isolated milk proteins in allergic children. Pediatrics. 32: 425–443.
Hambling SG, McAlpine AS, Sawyer L. 1992.β-Lactoglobulin in Advanced Dairy Chemistry-I: Proteins. P. F. Fox, ed. 140–191.
Hamosh M. 1996. Digestion in the newborn. Clin Perinatol. 23:191–209.
Harris BL. 1997. Selection to increaseβ-lactoglobulin B variant in New Zealand dairy cattle. in Milk Protein Polymorphism. J. P. Hill and M. Boland, eds. International Dairy. 467–473.
Havea, PH. Singh, and LK Creamer. 2001. Characterization of heat-induced aggregates of β-lactoglobulin,α-lactalbumin, and bovine serum albumin in a whey protein concentrate environment. J. Dairy Res. 68:483–497.
Hefle S L, Taylor S L .2004. Food allergy and the food industry Curr. Allergy Asthma Rep. 4:55–59.
Heine RG, Elsayed S, Hosking CS, Hill DJ. 2002. Cow’s milk allergy in infancy. Curr Opin Allergy Clin Immunol. 2(3):217-225.
Helm RM, Furuta GT, Stanley JS, Ye J, Cockrell G, Connaughton C, Simpson P, Bannon GA, Burks AW. 2002. A neonatal swine model for peanut allergy. J Allergy Clin Immunol.109(1): 136-142.
Herz U, Joachim R, Ahrens B, Scheffold A, Radbruch A , Renz H. 2001. Allergic sensitization and allergen exposure during pregnancy favor the development of atopy in the neonate. Int Arch Allergy Immunol. 124(1-3): 193-6.
Hill, JP, M. Boland and AF Smith. 1997. The effect ofβ-lactoglobulin variants on milk powder manufacture and properties. Pages 372–394 in Milk Protein Polymorphism. J. P. Hill and M. Boland, ed. International Dairy Federation, Brussels, Belgium.
H?st A, Halken S. 1990. A prospective study of cow milk allergy in Danish infants during the first 3 years of life. Clinical course in relation to clinical and immunological type of hypersensitivity reaction. Allergy. 45(8):587-596.
H?st A, Husby S, Osterballe O. 1988. A prospective study of cow’s milk allergy in exclusively breast-fed infants. Incidence, pathogenetic role of early inadvertent exposure to cow′s milk formula, and characterization of bovine milk protein in human milk. Acta Paediatr Scand; 77(5):663-70.
H?st A. 1994. Cow’s milk protein allergy and intolerance in infancy. Some clinical, epidemiological and immunological aspects. Pediatr Allergy Immunol. 5(5 Suppl):1-36.
H?st A. 2002. Frequency of cow’s milk allergy in childhood. Ann Allergy Asthma Immunol. 89 (6 Suppl I):33-37.
Iametti S, De Gregori B, Vecchio G, Bonomi F. 1996. Modifications occur at different structural levels during the heat denaturation of beta-lactoglobulin. Eur J Biochem .237(1): 106-112.
Ignatowski TA, Bidlack JM. 1999. Differential kappa-opioid receptor expression on mouse lymphocytes at varying stages of maturation and on mouse macrophages after selective elicitation. The Journal of Pharmacology and Experimental Therapeutics. 290: 863-870.
Imaizumi A, Kawakami T, Murakami F, Soma Y, Mizoguchi M. 2003. Effective treatment of pruritus in atopic dermatitis using H1 antihistamines (second-generation antihistamines): changes in blood histamine and tryptase levels. Journal of Dermatological Science. 33 (1):23-29.
Inoue R, Matsushita S, Kaneko H, Shinoda S, Sakaguchi H, Nishimura Y, Kondo N.2001. Identification of beta-lactoglobulin-derived peptides and class II HLA molecules recognized by T cells from patients with milk allergy. Clin Exp Allergy. 31 (7): 1126-1134.
Ishizaka T, Tomioka H, Ishizaka K. 1971. Degranulation of human basophil leukocytes by anti-g E antibody. J Immunol.106:705-710.
Jakobsson I, Lothe L, Borschel MW. 2000. Effectiveness of casein hydrolysate feedings in infants with colic. Acta Paediatr. 89 (1):18-21.
Jakobsson O, Lindberg T. 1979. A prospective study of cow’s milk protein intolerance in Swedish infants. Acta Paediatr Scand. 68 (6):853-859.
Jameson G B, Adams JJ, Creamer LK. 2002. Flexibility, functionality and hydrophobicity of bovineβ-lactoglobulins. Int Dairy J. 12:319–329.
Jarvinen KM, Beyer K, Vila L, Chatchatee P, Busse PJ, Sampson HA. 2002. B-cell epitopes as a screening instrument for persistent cow’s milk allergy. J Allergy Clin Immunol. 110 (2): 293–297.
Jarvinen KM, Chatchatee P, Bardina L, Beyer K, Sampson HA. 2001. IgE and IgG binding epitopes on alpha-lactalbumin and betalactoglobulin in cow’s milk allergy. Int Arch Allergy Immunol. 126 (2); 111–118.
Ju HR, Okumiya M, Nishizono S, Ki M, Sugano M, Imaizumi K.1997. Increase in degranulation of mucosal mast cells in rats sensitized with milk whey protein hydrolysates compared with native proteins. Food Chem Toxicol. 35(7): 663-668.
Karamanova L, Fukal L, Kodicek M, Rauch P, Mills E, Morgan M. 2003. Effect of Heat Treatment on the Detection of Intact Bovineβ-Lactoglobulins by LC Mass Spectrometry. Food Agric Immunol. 15:77–91
Karine APC. Creminon H, Bernard G, Clement L, Negronil Y, Frobert J, Grassi, Wal JM. 2000. Evaluation of a high IgE-responder mouse model of allergy to bovineβ- lactoglobulin: development of sandwich immunoassays for total and allergen-specific IgE, IgG1 and IgG2a in β-lg-sensitized mice. Journal of Immunological Methods. 235:21–32.
Kato C, Sato K, Eishi Y, Nakamura K. 1999. The influence of initial exposure timing to beta-lactoglobulin on oral tolerance induction. J Allergy Clin Immunol. 104(4 Pt 1): 870-878.
Kimura K, Adachi M, Kubo K, Ikemoto Y.1999. The basal plasma histamine level andeosinophil count in allergic and non-allergic patients. Fukuoka Igaku Zasshi. 90 (12): 457-463.
Kinsella JE, and D M Whitehead. 1989. Proteins in whey: Chemical, physical and functional properties. Adv Food Nutr Res. 33:343–438.
Kitabatake N, Kinekawa Y. 1998. Digestibility of Bovine Milk Whey Protein and β-Lactoglobulin in Vitro and in Vivo. J Agric Food Chem. 46 (12): 4917-4923.
Kitagawa S, Zhang S, Harari Y, Castro GA. 1995. Relative allergenicity of cow's milk and cow's milk-based formulas in an animal model. Am J Med Sci. 310 (5): 183-187.
Klemola T, Vanto T, Juntunen-Backman K, Kalimo K, Korpela R, Varjonen E. 2002. Allergy to soy formula and to extensively hydrolyzed whey formula in infants with cow’s milk allergy: a prospective, randomized study with a follow-up to the age of 2 years. J Pediatr. 140 (2):219-224.
Knippels LM, Houben GF, Spanhaak S, Penninks AH. 1999a. An oral sensitization model in Brown Norway rats to screen for potential allergenicity of food proteins. Methods. 19 (1): 78-82.
Knippels LM, Penninks AH, Spanhaak S, Houben GF. 1998b. Oral sensitization to food proteins: a Brown Norway rat model. Clin Exp Allergy. 28(3): 368-375.
Knippels LM, Penninks AH, van Meeteren M, Houben GF. 1999c. Humoral and cellular immune responses in different rat strains on oral exposure to ovalbumin. Food Chem Toxicol. 37 (8): 881-888.
Knippels LMJ, Penninks AH, Smit JJ, Houben GF. 1999d. Immune-Mediated Effects upon Oral Challenge of Ovalbumin-Sensitized Brown Norway Rats: Further Characterization of a Rat Food Allergy Model. Toxicol Appl Pharmaco.l 156 (3): 161-169.
Kobayashi K, Hirano A, Ohta A, Yoshida T, Takahashi K, Hattori M. 2001. Reduced immunogenicity of beta-lactoglobulin by conjugation with carboxymethyl dextran differing in molecular weight. Journal of Agricultural and Food Chemistry. 49: 823~831.
Kobayashi T, Ikeguchi M, Sugai S. 2000. Molten globule structure of equineβ-lactoglobulin probed by hydrogen exchange. J Mol Biol. 299:757–770.
Koldovsky O. 1984. J Am Coll Nutr. 3:131–138
Koshibu T. 1994. Measurement of plasma histamine, urinary N-methylhistamine and peripheral eosinophil counts in food provocation tests in infants and children with atopic dermatitis. Arerugi. 43 (7):787-795.
Kraulis PJ. 1991. MOLSCRIPT—A program to produce both detailed and schematic plots of protein structures. J Appl Cryst. 24:946–950.
Kurisaki J, Nakamura S, Kaminogawa S, Yamauchi K.1982. The antigenic properties of β-lactoglobulins examined with mouse IgE antibody. Agric Biol Chem. 4: 2069-2075.
Kuwata K, M Hoshino, S Era, C A Batt, Y Goto. 1998. Theα-βtransition ofβ-lactoglobulin as evidenced by heteronuclear NMR. J. Mol. Biol. 283:731–739.
Lara V.F, M. Olivares, and J. Xaus. 2005. The balance between caseins and whey proteins in cow’s milk determines its allergenicity. J. Dairy Sci. 88:1654-1660.
Lee YH. 1992. Food-processing approaches to altering allergenic potential of milk-basedformula J Pediatr. 121:47–50.
Li XM, Schofied BH, Huang CK, Kleiner GI, Sampson HA. 1999. A murine model of IgE-mediated cow’s milk hypersensitivity. J Allergy Clin Immunol. 103:206-214.
Lombardi G, Miglio G, Dianzani C, Mesturini R, Varsaldi F, Chiocchetti A, et al. 2004. Glutamate modulation of human lymphocyte growth: In vitro studies, Biochemical and Biophysical Research Communications. 318:496-502.
Lyster RLJ. 1972. Reviews of the progress of dairy science. Section C. Chemistry of milk proteins. J Dairy Res. 39:279–318.
Mahmud R, Matn MA, Otani H. 2004. Mitogenic effect of bovine b-lactoglobulin and its proteolytic digests on mouse spleen resting cells. Pakistan Journal of Biological Sciences. 7(12): 2045-2050.
Mailliart P, Ribadeau-Dumas B. 1988. Preparation of B-Lactoglobulin And B-Lactoglobulin Free Proteins From Whey Retentate By NaCl Salting Out At Low pH. Journal of Food Science.53: 743-745.
M?kinen-Kiljunen S, Palosuo T. 1992. A sensitive enzyme-linked immunosorbent assay for determination of bovine beta-lactoglobulin in infant feeding formulas and in human milk. Allergy. 47 (4 Pt 2):347-352.
Mansouri A, Gueant JL, Capiaumont J, Pelosi P, Nabet P, Haertle T. 1998. Plasma membrane receptor for beta-lactoglobulin and retinol-binding protein in murine hybridomas. Biofactors. 7(4): 287-298.
Mansouri A, Haertle T, Gerard A, Gerard H, Gueant JL. 1997. Retinol free and retinol complexed beta-lactoglobulin binding sites in bovine germ cells. Biochim Biophys Acta. 1357(1): 107-114.
Martelli A, De Chiara A, Corvo M, Restani P, Fiocchi A. 2002. Beef allergy in children with cow’s milk allergy; cow’s milk allergy in children with beef allergy. Ann Allergy Asthma Immunol. 89(6 Suppl 1):38-43.
Martin TR, Galli SJ, Katona IM, Drazen JM. 1989. Role of mast cells in anaphylaxis. Evidence for the importance of mast cells in the cardiopulmonary alterations and death induced by anti-IgE in mice. J Clin Invest. 83:1375-1383.
Maynard F, Jost R, Wal JM. 1997. Human IgE binding capacity of tryptic peptides from bovine alpha–lactalbumin. Int Arch Allergy Immunol. 113:478–488.
McKenzie HA, Sawyer WH. 1967. Effect of pH onβ-lactoglobulins. Nature 214:1101–1104.
McLain BI, Cameron DJ, Barnes GL. 1994. Is cow’s milk protein intolerance a cause of gastro-oesophageal reflux in infancy? J Paeditr Child Health. 30(4):316-318.
Mercier A, Gauthier SF, Fliss I. 2004. Immunomodulating effects of whey proteins and their enzymatic digests. International Dairy Journal. 14:175-183.
Miller K, Laugee J, Meredith C.1998. The monitoring of the effects of food components on immunoreactivity in experimental animals. Allergy. 53 (46 Suppl): 35-37.
Miller K, Meredith C, Selo I, Wal JM. 1999. Allergy to bovine beta-lactoglobulin: specificity of immunoglobulin E generated in the Brown Norway rat to tryptic and synthetic peptides. Clin Exp Allergy. 29 (12): 1696-1704.
Miyauchi H, Kaino A, Shinoda I, Fukuwatari Y, Hayasawa H. 1997. Immunomodulatory effect of bovine lactoferrin pepsin hydrolysate on murine splenocytes and Peyer’s patch cells. Journal of Dairy Science. 80 (10):2330-2339.
Mizuno S, Nishimura S, Matsuura K, Gotou T, Yamamoto N. 2004. Release of short and proline-rich antihypertensive peptides from casein hydrolysate with an Aspergillus oryzae protease. J Dairy Sci. 87:3183–3188.
Monnai M, Horimoto Y, Otani H. 1998. Immunomodificatory effect of dietary bovine kappa-caseinoglycopeptide on serum antibody levels and proliferative responses of lymphocytes in mice. Milchwissenshaft. 53:129-132.
Muller-Renaud S, Dupont D, Dulieu P. 2004. Quantification of beta-casein in milk and cheese using an optical immunosensor. J Agric Food Chem. 52:659–664.
Murosaki S, Yamamoto Y, Ito K, Inokuchi T, Kusaka H, Ikeda H, Yoshikai Y. 1998.
Heat-killed Lactobacillus plantarum L-137 suppresses naturally fed antigen-specific IgE production by stimulation of IL-12 production in mice. J Allergy Clin Immunol. 102(1): 57-64.
Natale M, Bisson C, Monti G, Peltran A, Garoffo LP, Valentini S, Fabris C, Bertino E, Coscia A, Conti A. 2004. Cow’s milk allergens identification by two-dimensional immunoblotting and mass spectrometry. Mol Nutr Food Res. 48 (5):363–369.
Negroni L, Bernard H, Clement G, Chatel JM, Brune P, Frobert Y, Wal JM, Grassi J. 1998.
Two-site enzyme immunometric assays for determination of native and denatured beta-lactoglobulin. J Immunol Methods. 220: 25-37.
Nielsen BR, Poulsen OM, Hau J.1989. Reagin production in mice: effect of subcutaneous and oral sensitization with untreated bovine milk and homogenized bovine milk. In Vivo. 3(4): 271-274.
Oldfield DJ, Singh H, Taylor MW. 2005. Kinetics of heat-induced whey protein denaturation and aggregation in skim milks with adjusted whey protein concentration. J Dairy Res. 72(3): 369-378.
Oliveira KM, Valente-Mesquita VL, Botelho MM, Sawyer L, Ferreira ST, Polikarpov I. 2001. Crystal structures of bovine beta-lactoglobulin in the orthorhombic space group C222(1). Structural differences between genetic variants A and B and features of the Tanford transition. Eur J Biochem. 268 (2): 477-483.
Otani H, Uchio T, Tokita F. 1985. Antigenic reactivities of chemically modified β-lactoglobulins with antiserum to bovineβ-lactoglobulins. Agric Biol Chem. 49: 2531-2536.
Ouwehand AC, Salminen SJ, Skurnik M, Conway PL. 1997. Inhibition of Pathogen Adhesion by Beta-Lactoglobulin. Int Dairy J. 7(11): 685-692.
Paajanen L, Tuure T, Poussa T, Korpela R. 2003. No difference in symptoms during challenges with homogenized and unhomogenized cow's milk in subjects with subjective hypersensitivity tohomogenized milk. J Dairy Res. 70 (2): 175-179.
Paajanen L, Tuure T, Vaarala O, Korpela R. 2005. Homogenization of milk has no effect on milk-specific antibodies in healthy adults. Milchwissenschaft. 60 (3): 239-241.
Papiz MZ, Sawyer L, Eliopoulos EE, North AC, Findlay JB, Sivaprasadarao R, Jones TA, Newcomer ME, Kraulis PJ. 1986. The structure of beta-lactoglobulin and its similarity to plasma retinol-binding protein. Nature 324 (6095): 383-385.
Pecquet S, Bovetto L, Maynard F, Fritsche R. 2000. Peptides obtained by tryptic hydrolysis of bovine beta-lactoglobulin induce specific oral tolerance in mice. J Allergy Clin Immunol. 105(3): 514-521.
Penninks AH, Knippels LM. 2001. Determination of protein allergenicity: studies in rats. Toxicol Lett. 120(1-3): 171-180.
Perez MD, Sanchez L, Aranda P, Ena J, Oria R, Calvo M. 1992. Effect of beta-lactoglobulin on the activity of pregastric lipase. A possible role for this protein in ruminant milk. Biochim Biophys Acta. 1123(2): 151-155.
Piaial M, Antoinel JM, Guardia JAM. 2003. Assessment of the Benefits of Live Yogurt: Methods and Markers for in vivo Studies of the Physiological Effects of Yogurt Cultures. Microbial Ecology in Health and Disease. 15: 79-87
Pihlanto-Leppala A, Paakkari I, Rinta-Koski M, Antila P. 1997. Bioactive peptide derived from in vitro proteolysis of bovine beta-lactoglobulin and its effect on smooth muscle. J Dairy Res. 64(1): 149-155.
Pihlanto-Leppala A. 2000. Bioactive peptides derived from bovine whey proteins: opioid and ace-inhibitory peptides. Trends Food Sci Tech. 11(9-10): 347-356.
Plebani A, Restani P, Naselli A, Galli CL, Meini A, Cavagni G, Ugazio AG, Poiesi C. 1997.
Monoclonal and polyclonal antibodies against casein components of cow milk for evaluation of residual antigenic activity in 'hypoallergenic' infant formulas. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology. 27(8):949-956.
Poulsen OM, Hau J, Kollerup J. 1987. Effect of homogenization and pasteurization on the allergenicity of bovine milk analysed by a murine anaphylactic shock model. Clin Allergy. 17 (5): 449-458.
Poulsen OM, Nielsen BR, Basse A, Hau J.1990. Comparison of intestinal anaphylactic reactions in sensitized mice challenged with untreated bovine milk and homogenized bovine milk. Allergy. 45 (5): 321-326.
Puyol P, Perez MD, Sanchez L, Ena JM, Calvo M. 1995. Uptake and passage of beta-lactoglobulin, palmitic acid and retinol across the Caco-2 monolayer. Biochim Biophys Acta. 1236(1): 149-154.
Qi XL, Brownlow S, Holt C, Sellers P. 1995. Thermal denaturation of beta-lactoglobulin: effect of protein concentration at pH 6.75 and 8.05. Biochim Biophys Acta. 1248 (1): 43-49.
Qi XL, Holt C, McNulty D, Clarke DT, Brownlow S, Jones GR. 1997. Effect of temperatureon the secondary structure of beta-lactoglobulin at pH 6.7, as determined by CD and IR spectroscopy: a test of the molten globule hypothesis. Biochem J. 324 (Pt 1): 341-346.
Qin BY, Bewley MC, Creamer LK, Baker HM, Baker EN, Jameson GB. 1998. Structural basis of the Tanford transition of bovine beta-lactoglobulin. Biochemistry. 37(40): 14014-14023.
Reddy I, Kella N. Kinsella J. 1988. Structural and conformational basis of the resistance of beta-lactoglobulin to peptic and chymotryptic digestion. J Agric Food Chem.
Restani P, Gaiaschi A, Plebani A, Beretta B, Cavagni G, Fiocchi A. 1999. Cross-reactivity between milk proteins from different animal species. Clin Exp Allergy. 29(7):997-1004.
Restani P, Plebani A, Velona T, Cavagni G, Ugazio AG, Poiesi C, Muraro A, Galli CL. 1996.
Use of immunoblotting and monoclonal antibodies to evaluate the residual antigenic activity of milk protein hydrolysed formulae. Clin Exp Allergy 26:1182–1187.
Rico AI, Girones N, Fresno M, Alonso C, Requena JM. 2002. The heat shock proteins, Hsp70 and Hsp83, of Leishmania infantum are mitogens for mouse B cells. Cell Stress & Chaperones. 7: 339-346.
Ring J, Senter T, Cornell RC, Arroyave CM, Tan EM. 979. Plasma complement and histamine changes in atopic dermatitis. British Journal of Dermatology. 100 (5):521-530.
Roefs SP, De Kruif KG. 1994. A model for the denaturation and aggregation of beta-lactoglobulin. Eur J Biochem. 226(3): 883-889.
Rowland SJ. 1938. The Protein Distribution In Normal And Abnormal Milk. Journal of Dairy Research. 9:47-57.
Rozenfeld P, Docena GH, A?ón MC, Fossati CA. 2002. Detection and identification of a soy protein component that cross-reacts with caseins from cow’s milk. Clin Exp Immunol. 130(1):49-58.
Saarinen KM, Juntunen-Backman K, Jarvenpaa AL, Kuitunen P, Lope L, Renlund M, Siivola M, Savilahti E. 1999. Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants. J Allergy Clin Immunol. 104 (2 Pt 1): 457-461.
Saarinen KM, Juntunen-Backman K, J?venp?? AL, Klemetti P, Kuitunen P, Lope L. 2000. Breast-feeding and the development of cow′s milk protein allergy. Adv Exp Med Biol. 478:121-30.
Sakaguchi H, Inoue R, Kaneko H, Watanabe M, Suzuki K, Kato Z, Matsushita S, Kondo N. 2002. Interaction among human leucocyte antigen-peptide-T cell receptor complexes in cow's milk allergy: the significance of human leucocyte antigen and T cell receptor-complementarity determining region 3 loops. Clin Exp Allergy. 32 (5): 762-770.
Sakurai K, Goto Y. 2002. Manipulating monomer-dimer equilibrium of bovineβ-lactoglobulin by amino acid substitution. J. Biol. Chem. 277: 25735–25740.
Salvatore S, Vandenplas Y. 2002. Gastroesophageal reflux and cow milk allergy: is there a link? Pediatrics. 110 (5):972-984.
Sampson HA, Jolie PL. 1984. Increased plasma histamine concentrations after food challenges in children with atopic dermatitis. New England Journal of Medicine. 311(6): 372-376.
Sampson HA. 1999. Food allergy. Part 1: immunopathogenesis and clinical disorders. J Allergy Clin Immunol. 103(5 Pt 1): 717-728.
Sawyer L, Kontopidis G. 2000. The core lipocalin, bovine beta-lactoglobulin. Biochim Biophys Acta. 1482 (1-2): 136-148.
Sawyer L. 2003.β-Lactoglobulin. Pages 319–386 in Advanced Dairy Chemistry I, 3rd ed. P. F. Sawyer L. 2003.β-lactoglobulin. In: P. F. Fox and P. L. H. McSweeney (eds) Advanced dairy chemistry, Volume 1, 3rd Edn, Kluwer Academic/Plenum Publishers, 319-386.
Selo I, Clement G, Bernard H, Chatel J, Creminon C, Peltre G, Wal J. 1999. Allergy to bovine beta-lactoglobulin: specificity of human IgE to tryptic peptides. Clin Exp Allergy 29 (8): 1055 -1063.
Selo I, Negroni L, Creminon C, Yvon M, Peltre G, Wal JM. 1998. Allergy to bovine beta -lactoglobulin: specificity of human IgE using cyanogen bromide-derived peptides. Int Arch Allergy Immunol. 117 (1): 20-28.
Song CY, Chen WL, Yang MC, Huang JP, Mao SJ. 2005. Epitope mapping of a monoclonal antibody specific to bovine dry milk: involvement of residues 66-76 of strand D in thermal denatured beta-lactoglobulin. J Biol Chem. 280 (5): 3574-3582.
Takagi K, Teshima R, Okunuki H & Sawada J.2003. Comparative study of in vitro digestibility of food proteins and effect of preheating on the digestion. Biol Pharm Bulletin. 26(7): 969-973.
Tanford C, Bunville LG, Nozak Y i. 1959. The reversible transformation ofβ-lactoglobulin at pH 7.5. J Am Chem Soc. 81:4032–4036.
Tanford C, Taggart V. 1961. Ionization-linked Changes in Protein Conformation. II. The N–R Transition inβ-Lactoglobulin. J Amer Chem Soc. 83: 1634-1638.
Terpend K, Blaton MA, Candalh C, Wal JM, Pochart P, Heyman M. 1999. Intestinal barrier function and cow's milk sensitization in guinea pigs fed milk or fermented milk. J Pediatr Gastroenterol Nutr. 28(2): 191-198.
Tilley, J. M. A. 1960. The chemical and physical properties of bovineβ-lactoglobulin. Dairy Sci. Abstr. 22:111–125.
Totsuka M, Ametani A, Kaminogawa S. 1997. Fine mapping of T-cell determinants of bovine beta-lactoglobulin. Cytotechnology. 25(1-3): 101-113.
Tsuji NM, Kurisaki J, Mizumachi K, Kaminogawa S.1993. Localization of T-cell determinants on bovine beta-lactoglobulin. Immunol Lett. 37(2-3): 215-221.
Uhrinova S, Smith MH, Jameson GB, Uhrin D, Sawyer L, Barlow PN. 2000. Structural changes accompanying pH induced dissociation of theβ-lactoglobulin dimmer. Biochemistry 39: 3565–3574.
Valkonen KH, Rytk?nen J, Karttunen TJ, Kokkonen J, Alatossava T. 2002. Tools for analyzing immunological responses to betalactoglobulin in animal models: Significance of heat denaturation. In: T. Alatossava (ed) Immunological and Biochemical Tools for Analysis of Dairy Starters, Processes, and Products. Trivandrum, Kerala, India, Research Signpost, 125-137.
Villamiel M, Lopez-Fandino R, Corzo N, Olano A. 1997. Denaturation of beta-lactoglobulin and native enzymes in the plate exchanger and holding tube section during continuous flow pasteurization of milk. Food Chem. 58(1-2): 49-52.
von der Weid T, Bulliard C, Fritsche R.2001. Suppression of specific and bystander IgE responses in a mouse model of oral sensitization to beta-lactoglobulin. Int Arch Allergy Immunol. 125(4): 307-15.
Wong KF, Middleton N, Montgomery M, Dey M, Carr RI. 1998. Immunostimulation of murine spleen cells by materials associated with bovine milk protein fractions. Journal of Dairy Science. 81:1825–1832.
Wroblewska B, Karamc M, Amarowicz R. 2004. Immuorective properties of peptide fractions of cow whey milk proteins after enzymatic hydrolysis.International jouranl of food science and technology. 39:839-850.
Wróblewska BL, J?drychowski. 2005. Influence of Enzymatic Cow Milk Hydrolysates on IgA and IgG Response of Balb/c Mice Organism. Czech J Food Sci. 23:51-63.
Yamauchi R, Usui H, Yunden J, Takenaka Y, Tani F, Yoshikawa M. 2003. Characterization of beta-lactotensin, a bioactive peptide derived from bovine beta-lactoglobulin, as a neurotensin agonist. Biosci Biotechnol Biochem. 67(4): 940-943.