山茱萸提取物对compound 48/80诱导肥大细胞脱颗粒和血管通透性的抑制效应
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摘要
目的肥大细胞在过敏性疾病的病理生理中起重要作用，通过抑制肥大细胞的活化，在改善和预防过敏性疾病有着重要的实践意义。但山茱萸抗过敏作用机制尚不清楚。因此，利用能激活肥大细胞活性的物质，来研究山茱萸抗过敏作用的效能和药理机制。本研究目的是为揭示山茱萸对肥大细胞活化、血管通透性有无抑制作用及其抑制作用的机制。
方法利用大鼠腹腔肥大细胞，观察山茱萸提取物对compound 48／80诱导肥大细胞脱颗粒、组胺释放、细胞内钙摄入、cAMP量变化及血管通透性的作用。
结果山茱萸的前处理抑制了compound 48／80诱导肥大细胞脱颗粒、肥大细胞释放组胺、肥大细胞内钙摄入。山茱萸提取物增加了肥大细胞内cAMP水平，而compound 48／80引起cAMP水平减少被山茱萸提取物前处理抑制。而且山茱萸提取物前处理抑制了compound 48／80诱发皮肤反应时的血管通透性增加。
结论山茱萸提取物含有抑制compound 48／80诱导肥大细胞脱颗粒和血管通透性的成分。
OBJECTIVE The fruit of Corni fructus(CF), a perennial herb, is believed tohave anti-allergy effects, but its mechanism is unkown. The purpose of this studyis to investigate the inhibitory effect of CF on compound 48/80-induced mastcell activation.
METHODS For this, the effects of CF on the degranulation, the histaminerelease, the calcium influx and the change of the intracellular cAMP levels of ratperitoneal mast cells(RPMC) and influences of CF on the compound 48/80-induced cutaneous reation were studied.
RESULTS The results were as follows; the compound48/80-induceddegranulation, intracelluar calcium influx and histamine release of RPMC wassignificantly inhibited by pretreatment with CF,CF significantly inhibitedcompound 48/80-induced vascular permeability of rat cutaneous tissue. Fromthe above results.
CONCLUSIONS it is suggested that CF contains some substances whichinhibit the compound 48/80-induced vascular permeability and mast cellactivation.
方法利用大鼠腹腔肥大细胞，观察山茱萸提取物对compound 48／80诱导肥大细胞脱颗粒、组胺释放、细胞内钙摄入、cAMP量变化及血管通透性的作用。
结果山茱萸的前处理抑制了compound 48／80诱导肥大细胞脱颗粒、肥大细胞释放组胺、肥大细胞内钙摄入。山茱萸提取物增加了肥大细胞内cAMP水平，而compound 48／80引起cAMP水平减少被山茱萸提取物前处理抑制。而且山茱萸提取物前处理抑制了compound 48／80诱发皮肤反应时的血管通透性增加。
结论山茱萸提取物含有抑制compound 48／80诱导肥大细胞脱颗粒和血管通透性的成分。
OBJECTIVE The fruit of Corni fructus(CF), a perennial herb, is believed tohave anti-allergy effects, but its mechanism is unkown. The purpose of this studyis to investigate the inhibitory effect of CF on compound 48/80-induced mastcell activation.
METHODS For this, the effects of CF on the degranulation, the histaminerelease, the calcium influx and the change of the intracellular cAMP levels of ratperitoneal mast cells(RPMC) and influences of CF on the compound 48/80-induced cutaneous reation were studied.
RESULTS The results were as follows; the compound48/80-induceddegranulation, intracelluar calcium influx and histamine release of RPMC wassignificantly inhibited by pretreatment with CF,CF significantly inhibitedcompound 48/80-induced vascular permeability of rat cutaneous tissue. Fromthe above results.
CONCLUSIONS it is suggested that CF contains some substances whichinhibit the compound 48/80-induced vascular permeability and mast cellactivation.
引文
[1] Ludwyk R,Langunoff D:Drug inhibition of mast cell scecretion.Drug 29:277-289,1985
[2] Nilsson G, Costa JJ,Metcalfe DD:Mast cells and basophil,3th ed.Lippincott Williams &wilkins,Philadelphin,pp.97-117,1999.
[3] Tasaka K,Mio M,Izushi K,Aoki I:Role of the cytoskeletons on Ca~(2+)store of rat peritoneal mast cell.Skin pharmacol 4:43-52,1991.
[4] Sin TY, Kim SH,Lee ES,Eom DO,Kim HM: Action of Rubus coreanus extract on systemic and local anaphylaxis.Phytother Res 16:508-513,2002
[5] Lee MS,Ryu YG, Chai OK,kang KJ,lee JY:Inhibitory effect of polysaccharide fraction from Cotex Mori on compound 48/80-induced mast cell activation,Korean J Immunol 21:35-45,1999.
[6] Hachisuka H,Kusuhara M,Higuchi M,Okubo K, Sasaiy Y:Purification of rat cutaneous mast cells with percoll density centrifugation.Arch Dermatol Res 280:358-362,1988.
[7] Telkin V, Levi-schaffer F:Mechanism of tumour necrosis factor alpha mediatec eosinophil survival,Cytokine 15:20-26,2001
[8] 赵建军，马统勋．青霉噻唑蛋白致敏大鼠肥大细胞脱颗粒及组胺释放的变化[J]．中国药理学报，1989，1(1)：78—81
[9] Harvima RJ,Harvima IT, Fraki JE:Optimization of histamine radiolenzymatic assay with purified histamine N-methyltransferase.Clinica Chimica Acta 171:247-256,1988.
[10] Holmegaard SN: Measurement of cAMP in clinical investigations.Acta Endocrinologica 101:1-46,1982.
[11] 王钦富，王永奇，于超，等．炒紫苏子提取物的抗氧化作用研究[J]．中国药学杂志，2004，39(10)：745—747．
[12] Richard AG, Thomas JK,Barbara:kuby immunology,4th ed.freeman.pp.401-404,1999.
[13] Ischizaka T, Hirata F, Ishizaka K,Axelrode J:Stimulation of phospholipids methylation,Ca2+ influx and histamine rlease by bridging of IgE receptors on rat mast cells.Proc Natl Acad Sci USA 77:1903-1996,1980.
[14] William FG:Review of medical physiology, 14th ed.pp.30,1989.
[15] Sieghart W, Theorides TC,Greengard p,Douglas WW:Phosphorylation of a single mast cell protein in response to drug thst inhibit cecretion.Biochem pharmacy 30:2737-2745,1981.
[16] Theoharides TC,Sieghart W, Greengard P, Douglas WW:Antiallergic drug cromolyn may inhibit histamine secretion yb regulating phosphorylation of a mast cell protein.science 207:80-82,1980.
[17] Chang L, Kious T, Yougancioglu M, Killer D,Pfeiffer J;Cytoskeleton kf living,unstained ceils imaged by scanning force microscooy.Biophys J64:128-1293,1993.
[18] George WD,Steven MH,Edgar FK:Competitive inhibition kf compound 48/80-induced histamine release by Benzalkonium chloride and its analogogs and the polyamine receptor in mast cells.J Pharma Experi Ther 222:652-661,1982.
[19] Petersen LJ,Mosbech H,Skov p:allergen-induced histamine release in intact human skin in vivo asesed by skin microdialysis technique:characterization of factors influencing histamine releasability.J Allergy Clin Immunol 97:672-679,1996
[1] Renauld JC.New insights into the role of cytokines in asthma.J Clin Pathol.2001 ;54:577-89.
[2] Cookson w.The alliance of genes and environment in asthma and allergy. Nature 1999; 402:B5-11.
[3] Holt PG, Macaubas C, Stumbles PA, etal. The role of allergy in the development of asthma. Nature. 1999;402:B 12-7.
[4] Humbert M,Menz G, YingS,etal.The immunopathology of extrinsic (atopic) and intrinsic (non-atopic) asthma:more similarities than diferences.Immunol Today. 1999;20:528—33.
[5] Elias JA,Zhu Z,Chupp G, etal.Airway remodeling in asthma .J Clin Invest. 1999;104:1001-6.
[6] Jeffery PK,Airway pathology in asthma, basic mechanisms and clinical management.ed.by Barnes PJ, Rodger IW, Thomson NC.1998pp. 47-64. London, Academic Press.
[7] Kirshenbaum AS,Kessler SW, Gof JP, Metcalfe DD.Demonstration of the origin of human mast cells from CD34+bone marrow progenitor cells.J Immunol.1991 ;146:1410-5.
[8] Valent P, Bettelheim P.Cell surface structures on human basophils and mast cells:biochemical and functional characterization.Adv Immunol.1992;52:333-423.
[9] Rottem M,Okada T, Goff JP, Metcalfe DD.Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/Fc epsilon RI- cell population.Blood. 1994;84:2489-96.
[10] Yamaguchi M,Lantz CS,Oettgen HC, KatonaI M,Fleming T, Miyajima I,Kinet JP, Gali SJ.IgE enhances mouse mast cell Fc(epsilon) RI expression in vitro and invivo:evidence for anovel amplification mechanism in IgE-dependent reactions.J Exp Med. 1997; 185:663-72.
[11] Shimizu Y, IraniA M,Brown EJ,Ashman LK,Schwartz LB.Human mast cells derived from fetal liver cells cultured with stem cell factor express a functional CD51/CD61 (alha v beta3)integrin.Blood. 1995;86:930-9.
[12] Saito H,Ebisawa M,Tachimoto H,Shichijo M,Fukagawa K,Matsumoto K,Iikura Y, Awaji T, Tsujimoto G, Yanagida M, Uzumaki H,Takahashi G, Tsuji K, Nakahata T.Selective growth of human mast cells in duced by Steelfactor, IL-6, and prostaglandin E2 from cord blood mononuclear ceils. JImmunol. 1996;157:343-50.
[13] GaliS J,Dvorak AM, Dvorak HF. Basophils and mast cells :Morphologic insights into their biology, secretory pattems and function, prog. Allergy. 1984; 34:1-118.
[14] Benyon RC, Lowman MA,Church MK.Human skin mast cells:their dispersion,purification and secretory character ristics.J.Immunol.1987; 138: 861-867.
[15] Church MK,Caulfield JP.Mast cell and basophil functions.In Alergy.ed.by Holgate ST, Church MK. 1993 pp5.1-12.Gower Medical Publishing.London.
[16] Schwartz LB.Tryptase from human mast cells:Biochemistry, biology and clinical utility:In Neutra IProteases of Mast Cells.ed.by Schwartz LB.1990 pp90-113 Monogr.Ale rgy.Basel.Karge.
[17] Church MK,Benyon RC,Clegg LS,Holgate ST.Immunopharmacology of mast cells.In.Handbook of experimental pharmacology.ed.by Greaves MW, Schuster S. 1989 pp 129-166.Springer-VerlagBerlin Heidelberg.
[18] Caulfield JP, Lewis RA, H ein A,Austen KF.Secretion indissociated human pulmonary mast cells.Evidnece of solubilization of granule contents before discharge.J Cell Biol. 1980;85:299-311.
[19] Irani AA,Schechter NM,Craig SS,DeBlois G, Schwartz LB.Twotypes of human mast cells that have distinct neutral protease compositions.Proc Natl Acad Sci USA. 1986;83:4464-8.
[20] Goldstein SM,Kaempfer CE,Kealey JT, Wintroub BU.Huma mast cell carboxypeptidase. Purification and characterization. J.Clin.Invest. 1989; 83: 1630-1636.
[21] Irani AA,Schechter NM, Craig SS,etal.Two types of human mast cells that have distinct neutral protease compositions. Proc. Natl.Acad. Sci.USA. 1986; 83:4464-4468.
[22] Irani AA, Goldstein SM,Wintroub BU, Bradford T, Schwartz LB.Human mast cell carboxypeptidase.Selective localization to MCTC cells.J.Immunol. 1991;147:247-253.
[23] Holgate ST.The roleof mas tcells and basophils in inflammation.Clin Exp Allergy.2000;30 Suppl 1:28-32.
[24] Peters SP.Methanism of mast cell activation.In Asthma&Rhinitis.ed.byBusse WW, Holgate ST. 1995 pp 221-30 Blackwel, Oxford.
[25] Nagai S,Kitani S, Hirai K, Takaishi T, Nakajima K, Kihara H, Nonomura Y, Ito K,Morita Y.Pharmacological study of stem-cell-factor-induced mast cell histamine release with kinase inhibitors. Biochem Biophysic Res Commun. 1995;208:576-81.
[26] Okayama Y, Hunt TC, Kassel O, Ashman LK, Church MK. Assessment of theanti-c-kit monoclonal antibody YB5.B8 inafinity magnetic enrichment of human lung mast cells. J Immunol Methods. 1994; 169:153-61.
[27] Okayama Y, Benyon RC, Lowman MA, Church MK. In vitro effects of Hlantihistamine and PGD2 release from mast cells of human lung, tonsil, and skin. Alergy. 1994;49;246-53.
[28] 53.Postma DS,Bleecker ER,Amelung PJ,etal.Genetic susceptibility to asthmabronchial hyperresponsiveness coinherited with a major gene for atopy.N Engl J Med 1995;333:894-900.
[29] Miyajima I,Dombrowicz D,Martin TR,etal.Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc gammaRⅢ. Assessment of the cardiopulmonary changes,mast cell degranulation,and death associated with active or IgE-or IgG1-dependent passive anaphylaxis.JClin Invest. 1997;99:901-14.
[30] Scott T, Kaliner M.Mast cells in asthma.InThe mast cell in health and disease.ed.Kaliner MA,Metcalfe DD.1993 pp 575-608.New York, Marcel Dekker.
[31] Craig SS, DeBlois G, Schwartz LB.Mast cells in human keloid,smaU in testine,and lung by an immunoperoxidase technique using a murine monoclonal antibody against tryptase.Am J Pathol. 1986; 124:427-35.
[32] Broide DH,Eisman S,Ramsdel JW, Ferguson P, Schwartz LB,Wasserman SI.Airway evels of mast cell derived mediators in exercise-induced asthma.Am Rev Respir Dis. 1990; 141:563-8.
[33] Kawanami O,Ferrans VJ,Fulmer JD,Crystal RG.Ultrastructure of pulmonary mast cells in patients with fibrotic lung disorders.Lab.Invest. 198540:717-734.
[34] Liu MC, Hubbard WC, Proud D,Stealey BA,Gali SJ,Kagey-Sobotka A,Bleecker ER, Lichtenstein LM.Immediate and late inflammatory responses to ragweed antigen challenge of the peripheral airways in allergic asthmatics.Celular, mediator, andpermeability changes.Am Rev Respir Dis. 1991; 144:51-8.
[35] VanGanse E, Kaufman L,Derde MP, Yernault JC,Delaunois L,Vincken W.Efects of antihistamines in adult asthma:a meta-analysis of clinical trials.Eur Respir J.1997;10:2216-24.
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[2] Nilsson G, Costa JJ,Metcalfe DD:Mast cells and basophil,3th ed.Lippincott Williams &wilkins,Philadelphin,pp.97-117,1999.
[3] Tasaka K,Mio M,Izushi K,Aoki I:Role of the cytoskeletons on Ca~(2+)store of rat peritoneal mast cell.Skin pharmacol 4:43-52,1991.
[4] Sin TY, Kim SH,Lee ES,Eom DO,Kim HM: Action of Rubus coreanus extract on systemic and local anaphylaxis.Phytother Res 16:508-513,2002
[5] Lee MS,Ryu YG, Chai OK,kang KJ,lee JY:Inhibitory effect of polysaccharide fraction from Cotex Mori on compound 48/80-induced mast cell activation,Korean J Immunol 21:35-45,1999.
[6] Hachisuka H,Kusuhara M,Higuchi M,Okubo K, Sasaiy Y:Purification of rat cutaneous mast cells with percoll density centrifugation.Arch Dermatol Res 280:358-362,1988.
[7] Telkin V, Levi-schaffer F:Mechanism of tumour necrosis factor alpha mediatec eosinophil survival,Cytokine 15:20-26,2001
[8] 赵建军，马统勋．青霉噻唑蛋白致敏大鼠肥大细胞脱颗粒及组胺释放的变化[J]．中国药理学报，1989，1(1)：78—81
[9] Harvima RJ,Harvima IT, Fraki JE:Optimization of histamine radiolenzymatic assay with purified histamine N-methyltransferase.Clinica Chimica Acta 171:247-256,1988.
[10] Holmegaard SN: Measurement of cAMP in clinical investigations.Acta Endocrinologica 101:1-46,1982.
[11] 王钦富，王永奇，于超，等．炒紫苏子提取物的抗氧化作用研究[J]．中国药学杂志，2004，39(10)：745—747．
[12] Richard AG, Thomas JK,Barbara:kuby immunology,4th ed.freeman.pp.401-404,1999.
[13] Ischizaka T, Hirata F, Ishizaka K,Axelrode J:Stimulation of phospholipids methylation,Ca2+ influx and histamine rlease by bridging of IgE receptors on rat mast cells.Proc Natl Acad Sci USA 77:1903-1996,1980.
[14] William FG:Review of medical physiology, 14th ed.pp.30,1989.
[15] Sieghart W, Theorides TC,Greengard p,Douglas WW:Phosphorylation of a single mast cell protein in response to drug thst inhibit cecretion.Biochem pharmacy 30:2737-2745,1981.
[16] Theoharides TC,Sieghart W, Greengard P, Douglas WW:Antiallergic drug cromolyn may inhibit histamine secretion yb regulating phosphorylation of a mast cell protein.science 207:80-82,1980.
[17] Chang L, Kious T, Yougancioglu M, Killer D,Pfeiffer J;Cytoskeleton kf living,unstained ceils imaged by scanning force microscooy.Biophys J64:128-1293,1993.
[18] George WD,Steven MH,Edgar FK:Competitive inhibition kf compound 48/80-induced histamine release by Benzalkonium chloride and its analogogs and the polyamine receptor in mast cells.J Pharma Experi Ther 222:652-661,1982.
[19] Petersen LJ,Mosbech H,Skov p:allergen-induced histamine release in intact human skin in vivo asesed by skin microdialysis technique:characterization of factors influencing histamine releasability.J Allergy Clin Immunol 97:672-679,1996
[1] Renauld JC.New insights into the role of cytokines in asthma.J Clin Pathol.2001 ;54:577-89.
[2] Cookson w.The alliance of genes and environment in asthma and allergy. Nature 1999; 402:B5-11.
[3] Holt PG, Macaubas C, Stumbles PA, etal. The role of allergy in the development of asthma. Nature. 1999;402:B 12-7.
[4] Humbert M,Menz G, YingS,etal.The immunopathology of extrinsic (atopic) and intrinsic (non-atopic) asthma:more similarities than diferences.Immunol Today. 1999;20:528—33.
[5] Elias JA,Zhu Z,Chupp G, etal.Airway remodeling in asthma .J Clin Invest. 1999;104:1001-6.
[6] Jeffery PK,Airway pathology in asthma, basic mechanisms and clinical management.ed.by Barnes PJ, Rodger IW, Thomson NC.1998pp. 47-64. London, Academic Press.
[7] Kirshenbaum AS,Kessler SW, Gof JP, Metcalfe DD.Demonstration of the origin of human mast cells from CD34+bone marrow progenitor cells.J Immunol.1991 ;146:1410-5.
[8] Valent P, Bettelheim P.Cell surface structures on human basophils and mast cells:biochemical and functional characterization.Adv Immunol.1992;52:333-423.
[9] Rottem M,Okada T, Goff JP, Metcalfe DD.Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/Fc epsilon RI- cell population.Blood. 1994;84:2489-96.
[10] Yamaguchi M,Lantz CS,Oettgen HC, KatonaI M,Fleming T, Miyajima I,Kinet JP, Gali SJ.IgE enhances mouse mast cell Fc(epsilon) RI expression in vitro and invivo:evidence for anovel amplification mechanism in IgE-dependent reactions.J Exp Med. 1997; 185:663-72.
[11] Shimizu Y, IraniA M,Brown EJ,Ashman LK,Schwartz LB.Human mast cells derived from fetal liver cells cultured with stem cell factor express a functional CD51/CD61 (alha v beta3)integrin.Blood. 1995;86:930-9.
[12] Saito H,Ebisawa M,Tachimoto H,Shichijo M,Fukagawa K,Matsumoto K,Iikura Y, Awaji T, Tsujimoto G, Yanagida M, Uzumaki H,Takahashi G, Tsuji K, Nakahata T.Selective growth of human mast cells in duced by Steelfactor, IL-6, and prostaglandin E2 from cord blood mononuclear ceils. JImmunol. 1996;157:343-50.
[13] GaliS J,Dvorak AM, Dvorak HF. Basophils and mast cells :Morphologic insights into their biology, secretory pattems and function, prog. Allergy. 1984; 34:1-118.
[14] Benyon RC, Lowman MA,Church MK.Human skin mast cells:their dispersion,purification and secretory character ristics.J.Immunol.1987; 138: 861-867.
[15] Church MK,Caulfield JP.Mast cell and basophil functions.In Alergy.ed.by Holgate ST, Church MK. 1993 pp5.1-12.Gower Medical Publishing.London.
[16] Schwartz LB.Tryptase from human mast cells:Biochemistry, biology and clinical utility:In Neutra IProteases of Mast Cells.ed.by Schwartz LB.1990 pp90-113 Monogr.Ale rgy.Basel.Karge.
[17] Church MK,Benyon RC,Clegg LS,Holgate ST.Immunopharmacology of mast cells.In.Handbook of experimental pharmacology.ed.by Greaves MW, Schuster S. 1989 pp 129-166.Springer-VerlagBerlin Heidelberg.
[18] Caulfield JP, Lewis RA, H ein A,Austen KF.Secretion indissociated human pulmonary mast cells.Evidnece of solubilization of granule contents before discharge.J Cell Biol. 1980;85:299-311.
[19] Irani AA,Schechter NM,Craig SS,DeBlois G, Schwartz LB.Twotypes of human mast cells that have distinct neutral protease compositions.Proc Natl Acad Sci USA. 1986;83:4464-8.
[20] Goldstein SM,Kaempfer CE,Kealey JT, Wintroub BU.Huma mast cell carboxypeptidase. Purification and characterization. J.Clin.Invest. 1989; 83: 1630-1636.
[21] Irani AA,Schechter NM, Craig SS,etal.Two types of human mast cells that have distinct neutral protease compositions. Proc. Natl.Acad. Sci.USA. 1986; 83:4464-4468.
[22] Irani AA, Goldstein SM,Wintroub BU, Bradford T, Schwartz LB.Human mast cell carboxypeptidase.Selective localization to MCTC cells.J.Immunol. 1991;147:247-253.
[23] Holgate ST.The roleof mas tcells and basophils in inflammation.Clin Exp Allergy.2000;30 Suppl 1:28-32.
[24] Peters SP.Methanism of mast cell activation.In Asthma&Rhinitis.ed.byBusse WW, Holgate ST. 1995 pp 221-30 Blackwel, Oxford.
[25] Nagai S,Kitani S, Hirai K, Takaishi T, Nakajima K, Kihara H, Nonomura Y, Ito K,Morita Y.Pharmacological study of stem-cell-factor-induced mast cell histamine release with kinase inhibitors. Biochem Biophysic Res Commun. 1995;208:576-81.
[26] Okayama Y, Hunt TC, Kassel O, Ashman LK, Church MK. Assessment of theanti-c-kit monoclonal antibody YB5.B8 inafinity magnetic enrichment of human lung mast cells. J Immunol Methods. 1994; 169:153-61.
[27] Okayama Y, Benyon RC, Lowman MA, Church MK. In vitro effects of Hlantihistamine and PGD2 release from mast cells of human lung, tonsil, and skin. Alergy. 1994;49;246-53.
[28] 53.Postma DS,Bleecker ER,Amelung PJ,etal.Genetic susceptibility to asthmabronchial hyperresponsiveness coinherited with a major gene for atopy.N Engl J Med 1995;333:894-900.
[29] Miyajima I,Dombrowicz D,Martin TR,etal.Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc gammaRⅢ. Assessment of the cardiopulmonary changes,mast cell degranulation,and death associated with active or IgE-or IgG1-dependent passive anaphylaxis.JClin Invest. 1997;99:901-14.
[30] Scott T, Kaliner M.Mast cells in asthma.InThe mast cell in health and disease.ed.Kaliner MA,Metcalfe DD.1993 pp 575-608.New York, Marcel Dekker.
[31] Craig SS, DeBlois G, Schwartz LB.Mast cells in human keloid,smaU in testine,and lung by an immunoperoxidase technique using a murine monoclonal antibody against tryptase.Am J Pathol. 1986; 124:427-35.
[32] Broide DH,Eisman S,Ramsdel JW, Ferguson P, Schwartz LB,Wasserman SI.Airway evels of mast cell derived mediators in exercise-induced asthma.Am Rev Respir Dis. 1990; 141:563-8.
[33] Kawanami O,Ferrans VJ,Fulmer JD,Crystal RG.Ultrastructure of pulmonary mast cells in patients with fibrotic lung disorders.Lab.Invest. 198540:717-734.
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