妊娠期高血压疾病中趋化因子LKN-1及其受体CCR1和CCR3的表达
摘要
目的:妊娠期高血压疾病是导致孕产妇及围产儿发病率和死亡率增加的重要因素之一。但目前对该病发病机制的研究尚不清楚,现广泛认为子痫前期-子痫的发病起源于胎盘病理生理改变,胎盘血管的免疫、炎性应答等因素导致全身小动脉痉挛,进一步导致全身血管内皮细胞损伤,后者引起子痫前期的一系列临床症状。在胎盘组织的母体-胎儿面致炎和抗炎的因子(例如:细胞因子、趋化因子、黏附分子、信号转导因子、生长因子和受体等)可能部分参与病变的发病。趋化因子是一类结构和功能相关的多肽超家族,按照一级肽链结构特点分为CXC、CC、C和CX3C四个亚家族,在白细胞向炎症部位趋化和随后的活化过程中起重要作用。研究表明,趋化因子与胎盘血管炎性病变密切相关:白介素-8(IL-8)、RANTES、单核细胞趋化蛋白-1(MCP-1)等趋化因子己证实在胎盘血管病变中表达升高,在炎性病变进展过程中起着促进作用。趋化因子Leukotactin-1(LKN-1)属CC亚家族一员,研究发现,LKN-1可通过其受体CCR1、CCR3诱导人内皮细胞趋化反应,还可促内皮细胞分化、诱导体内外血管生成,在血管炎性病变——动脉粥样硬化斑块中表达显著增高。而妊娠期高血压疾病患者胎盘绒毛血管和胎盘床螺旋动脉多可见发生急性动脉粥样化的改变,因此,我们推测妊娠期高血压疾病的发生可能与胎盘血管中LKN-1的表达相关,本文通过测定妊娠期高血压疾病患者胎盘组织中LKN-1及其受体CCR1和CCR3的表达,以探讨它们在妊娠期高血压疾病发病中的作用。
材料和方法:收集32例妊娠期高血压疾病患者(研究组)和32例正常足月妊娠孕妇(正常对照组)的胎盘组织;采用Western蛋白印记法检测LKN-1及其受体CCR1和CCR3在胎盘组织中的表达;并用免疫组化法对LKN-1、CCR1和CCR3的表达进行定位。
结果:1.Western蛋白印记法示:在研究组和正常对照组胎盘组织中LKN-1蛋白表达均为阴性;研究组CCR1蛋白水平明显低于正常对照组(0.6608±0.0582vs 0.8806±0.0324)(P＜0.01);研究组胎盘组织中CCR3蛋白水平明显低于正常对照组(0.1695±0.0146 vs 0.2725±0.0057)(P＜0.01)。
2.免疫组化法示:两组孕妇胎盘组织中LKN-1表达均为阴性;两组孕妇胎盘组织中基质细胞及血管内皮细胞内均有CCR1阳性表达,绒毛滋养细胞中CCR1弱阳性表达;两组孕妇胎盘绒毛滋养细胞及血管内皮细胞内均有CCR3阳性表达。
结论:LKN-1在妊娠期高血压疾病患者和正常足月妊娠的胎盘组织中均无阳性表达;而其受体CCR1与CCR3水平下调与妊娠期高血压疾病的发生、发展有密不可分的关系。
Objective Hypertensive disorder complicating pregnancy plays an important part in the raising of the morbidity and mortality of gravida and fetus.And its pathogenesis is still unclear now.It's presumed that pathophysiological change is the origin of eclampsism-eclampsia.The immune and inflammatory reaction etc.induce the spasmus of systemic arterioles,which causes the damage of systemic vascular endothelial cells,then provokes a serial of clinic symptoms.Phlogogenic factors and anti-inflammatory factors existing in the placenta such as cytokines,chemokines, adhesion molecules,signal transduction factors,growth factors and their receptors maybe take part in the pathogenesis.Chemokines are a group of polypeptides which play a great role in chemotactic and activatory responses of leukocytes.According to the construction features of their first class peptide chains,they are divided into four subfamilies,such as CXC,CC,C and CX3C.It's showed that chemokines are related to inflammatory changes in placental vessels,and such as IL-8,RANTES,MCP-1 et al.are confirmed to go up in placental vasal diseases and promote the progression of inflammation.Leukotactin-1(LKN-1)belongs to the CC subfamily,and through its receptors(CCR1 and CCR3)it can induce the chemotactic response of human endothelial cells,promote the differentiation of endothelial cells and induce the formation of vessels.And in atherosclerotic plaque its expression is obviously elevated.As we see,acute atherosclerosis takes place in the vessels of placental villus and helicine arteries of the hypertensive disorder complicating pregnancy patients, thus we presume the pathogenesis of hypertensive disorder complicating pregnancy is related to the expression of LKN-1 in placental vessels.Here we detected the expression of LKN-1 and CCR1,CCR3 in the placenta of hypertensive disorder complicating pregnancy patients to investigate the role of LKN-1,CCR1 and CCR3 in the pathogenesis of hypertensive disorder complicating pregnancy.
Methods The level of LKN-1,CCR1 and CCR3 in placenta was detected from 32 patients with hypertensive disorder complicating pregnancy(hypertensive disorder complicating pregnancy group)and 32 nomal pregnant women(normal control group) by western blot(WB)and the expression of LKN-1,CCR1 and CCR3 in the two groups was detected by immunohistochemistry(IHC).
Results 1.Western blot showed LKN-1 was negative in the placentas from the two groups;while CCR1 from hypertensive disorder complicating pregnancy group was significantly lower than that in normal control group(0.6608±0.0582 vs 0.8806±0.0324)(P＜0.01);and CCR3 from hypertensive disorder complicating pregnancy group was significantly lower than that in normal control group(0.1695±0.0146 vs 0.2725±0.0057)(P＜0.01).
2.IHC showed LKN-1 was negative in the placentas from the two groups;CCR1 was expressed in the stromal cells and the vascular endothelial cells in both groups, and weak signal was found associated with the trophoblast layer;while CCR3 was expressed in the trophoblast cells and the vascular endothelial cells in both groups.
Conclusion LKN-1 was negative in the placentas from the two groups.The down regulation of CCR1 and CCR3 was related to the occurrence and development of hypertensive disorder complicating pregnancy.
材料和方法:收集32例妊娠期高血压疾病患者(研究组)和32例正常足月妊娠孕妇(正常对照组)的胎盘组织;采用Western蛋白印记法检测LKN-1及其受体CCR1和CCR3在胎盘组织中的表达;并用免疫组化法对LKN-1、CCR1和CCR3的表达进行定位。
结果:1.Western蛋白印记法示:在研究组和正常对照组胎盘组织中LKN-1蛋白表达均为阴性;研究组CCR1蛋白水平明显低于正常对照组(0.6608±0.0582vs 0.8806±0.0324)(P＜0.01);研究组胎盘组织中CCR3蛋白水平明显低于正常对照组(0.1695±0.0146 vs 0.2725±0.0057)(P＜0.01)。
2.免疫组化法示:两组孕妇胎盘组织中LKN-1表达均为阴性;两组孕妇胎盘组织中基质细胞及血管内皮细胞内均有CCR1阳性表达,绒毛滋养细胞中CCR1弱阳性表达;两组孕妇胎盘绒毛滋养细胞及血管内皮细胞内均有CCR3阳性表达。
结论:LKN-1在妊娠期高血压疾病患者和正常足月妊娠的胎盘组织中均无阳性表达;而其受体CCR1与CCR3水平下调与妊娠期高血压疾病的发生、发展有密不可分的关系。
Objective Hypertensive disorder complicating pregnancy plays an important part in the raising of the morbidity and mortality of gravida and fetus.And its pathogenesis is still unclear now.It's presumed that pathophysiological change is the origin of eclampsism-eclampsia.The immune and inflammatory reaction etc.induce the spasmus of systemic arterioles,which causes the damage of systemic vascular endothelial cells,then provokes a serial of clinic symptoms.Phlogogenic factors and anti-inflammatory factors existing in the placenta such as cytokines,chemokines, adhesion molecules,signal transduction factors,growth factors and their receptors maybe take part in the pathogenesis.Chemokines are a group of polypeptides which play a great role in chemotactic and activatory responses of leukocytes.According to the construction features of their first class peptide chains,they are divided into four subfamilies,such as CXC,CC,C and CX3C.It's showed that chemokines are related to inflammatory changes in placental vessels,and such as IL-8,RANTES,MCP-1 et al.are confirmed to go up in placental vasal diseases and promote the progression of inflammation.Leukotactin-1(LKN-1)belongs to the CC subfamily,and through its receptors(CCR1 and CCR3)it can induce the chemotactic response of human endothelial cells,promote the differentiation of endothelial cells and induce the formation of vessels.And in atherosclerotic plaque its expression is obviously elevated.As we see,acute atherosclerosis takes place in the vessels of placental villus and helicine arteries of the hypertensive disorder complicating pregnancy patients, thus we presume the pathogenesis of hypertensive disorder complicating pregnancy is related to the expression of LKN-1 in placental vessels.Here we detected the expression of LKN-1 and CCR1,CCR3 in the placenta of hypertensive disorder complicating pregnancy patients to investigate the role of LKN-1,CCR1 and CCR3 in the pathogenesis of hypertensive disorder complicating pregnancy.
Methods The level of LKN-1,CCR1 and CCR3 in placenta was detected from 32 patients with hypertensive disorder complicating pregnancy(hypertensive disorder complicating pregnancy group)and 32 nomal pregnant women(normal control group) by western blot(WB)and the expression of LKN-1,CCR1 and CCR3 in the two groups was detected by immunohistochemistry(IHC).
Results 1.Western blot showed LKN-1 was negative in the placentas from the two groups;while CCR1 from hypertensive disorder complicating pregnancy group was significantly lower than that in normal control group(0.6608±0.0582 vs 0.8806±0.0324)(P＜0.01);and CCR3 from hypertensive disorder complicating pregnancy group was significantly lower than that in normal control group(0.1695±0.0146 vs 0.2725±0.0057)(P＜0.01).
2.IHC showed LKN-1 was negative in the placentas from the two groups;CCR1 was expressed in the stromal cells and the vascular endothelial cells in both groups, and weak signal was found associated with the trophoblast layer;while CCR3 was expressed in the trophoblast cells and the vascular endothelial cells in both groups.
Conclusion LKN-1 was negative in the placentas from the two groups.The down regulation of CCR1 and CCR3 was related to the occurrence and development of hypertensive disorder complicating pregnancy.
引文
1.丰有吉,沈铿,等.妇产科学[M].第1版.北京:人民卫生出版社,2005,74-77.
2.Trudinger BJ,Giles WB,Cook CM,Bombardieri J,Collins L.Fetal umbilical artery flow velocity waveforms and placental resistance:Clinical significance.Br J Obstet Gynaecol 1985,92:23-30.
3.Wang X,Athayde N,Trudinger B.Placental vascular disease-A proinflammatory response of innate immunity.An J Obstet Gynecol 2003;189(6 suppl):S125.
4.Wang X,Athayde N,Trudinger B.Expression of toll-like receptor 4 in human endothelial cells stimulated by fetal plasma with umbilical placental vascular disease.J Soc Gynecol Investig 2003;10(2 suppl):#659.
5.Trudinger B,Wang J,Athayde N,Beutler L,Wang X.Association of umbilical placental vascular disease with fetal acute inflammatory cytokine responses.J Soc Gynecol Investig 2002;9:152-7.
6.Pober JS,Cotran RS.Cytokines and endothelial cell biology.Physiol Rev 1990;70:427-51.
7.Wang X,Athayde N,Trudinger B.Microvascular endothelial cell activation is present in the umbilical placental microcirculation in fetal placental vascular disease.Am J Obstet Gynecol 2004 Mar;190(3):596-601.
8.Hwang J,Kim CW,et al.Angiogenic activity of human CC chemokine CCL15 in vitro and in vivo.FEBS Lett.2004,570(1-3):47-51.
9.乐杰.妇产科学[M].第4版.北京:人民卫生出版社,1996:138-140.
10.莫娥清,刘穗玲.94例妊高征及其并发症分析.中国实用妇科与产科杂志.1996,12:215—216.
11.Fernandez-Botran R,Chilton PM,Ma Y.Soluble cytokine receptors:their roles in immunoregulation,disease,and therapy.Adv Immunol,1996;63:269-336.
12.Jonsson Y,et al.Cytokine mapping of sera from women with preeclampsia and normal pregnancies.J Reprod Immunol.2006 Jun;70(1-2):83-91.
13.Tuomisto T,et al.Tumor suppressor and growth regulatory genes are overexpressed in severe early-onset preeclampsia--an array study on case-specific human preeclamptic placental tissue.Acta Obstet Gynecol Scand.2005 Jul;84(7):679-89.
14.Brewster JA,et al.Host inflammatory response profiling in preeclampsia using an in vitro whole blood stimulation model.Hypertens Pregnancy.2008;27(1):1-16.
15.Katabuchi H,et al.Characterization of macrophages in the decidual atherotic spiral artery with special reference to the cytology of foam cells.Med Electron Microsc.2003 Dec;36(4):253-62.
16.Lockwood CJ,et al.Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha and interleukin-lbeta in first trimester human decidual cells:implications for preeclampsia.Am J Pathol.2006Feb;168(2):445-52.
17.李翠兰等.重度妊娠高血压综合征患者子宫胎盘病理变化及其临床意义.中华妇产科杂志.2000,11:651.
18.Esther L,Birgit F,et al.Gene Profiling in Atherosclerosis Reveals a Key Role for Small Inducible Cytokines.Circulation.2005,111:3443-34.
19.Rina Yu,Chu-Sook Kim,et al.Involvement of leukotactin-1,a novel CC chemokine,in human atherosclerosis.Athrosclerosis.2004,174:35-42.
20.Won-Ha Lee,Se-Hwa Kim,et al.A novel chemokine,Leukotactin-1,induces chemotaxis,pro-atherogenic cytokines,and tissue factor expression in atherosclerosis.Atherosclerosis.2002,161:255-260.
21.Zlotnik A,et al.Immunity,2000,12:121-127.
22.Youn BS,Zhang SM,Lee EK,et al.Molecular cloning of leukotactin-1:a novel human beta-chemokine,a chemoa- ttractant for neutrophils,monocytes,and lymphocytes,and a potent agonist at CC chemokine recetpors 1 and 3.J Immunol,1997,159(11):5201.
23.Youn BS,Zhang SM,Broxmeyer HE,et al.Characterization of Ckbeta8 and Ckbeta8-1:two alternatively spliced forms of human beta-chemokine,chemoattractants for neutrophils,monocytes,and lynphocytes,and potent agonists at CC chemokine receptor 1.Blood,1998,91(9):3118.
24.Lee JK,Lee EH,Yun YP,et al.Truncation of NH2-terminal Amino Acid Residues Increases Agonistic Potency of Leukotactin-1 on CC.Chemokine Receptors 1 and 3.J Biol Chem,2002,277(17):14757.
25.Zhang SM,Youn BS,Gao JL,et al.Differential Effects of Leukotactin-1 and Macrophage Inflammatory Protein-1αon Neutrophils Mediated by CCR1.J Immunol,1999,162(8):4938.
26.Ko J,Kim IS,et al.Leukotactin-1/CCL15-induced chemotaxis signaling through CCR1 in HOS cells.FEBS Lett.2002,515(1-3):159-64.
27.Lee WH,Kim SH,Jeong EM,et al.A novel chemokine,Leukotactin-1,induces chemotaxis,pro-atherogenic cytokines,and tissue factor expression in atherosclerosis.Atherosclerosis,2002,161(2):255-60.
28.Richard Horuk.Chemokine receptors J.Cytokine Growth Factor Rev,2001,12(14):313-335.
29.Murdoch C,Finn A.Chemokine receptors and their role in inflammation and infectious diseases J.Blood,2000,95(10):3032-3043.
30.王健,赵金红.趋化因子受体研究进展.现代预防医学.2006,33(2):165.
31.James D,Frank M.Chemokine receptors A brief overview.Clinical and Applied Immunology Reviews.2000,1:105-125.
32.Sheikine Y,Hansson GK.Chemokines and atherosclerosis.Ann Med.2004,36(2):98-108.
33.Potteaux S,Combadière C,et al.Chemokine Receptor CCR1 Disruption in Bone Marrow Cells Enhances Atherosclerotic Lesion Development and Inflammation in Mice.Mol Med.2005,11(1-12):16-20.
1.Wang X,Athayde N,Trudinger B.Placental vascular disease-A proinflammatory response of innate immunity.An J Obstet Gynecol 2003;189(6 suppl):S125.
2.Wang X,Athayde N,Trudinger B.Expression of toll-like receptor 4 in human endothelial cells stimulated by fetal plasma with umbilical placental vascular disease.J Soc Gynecol Investig 2003;10(2 suppl):#659.
3.Trudinger B,Wang J,Athayde N,Beutler L,Wang X.Association of umbilical placental vascular disease with fetal acute inflammatory cytokine responses.J Soc Gynecol Investig 2002;9:152-7.
4.Pober JS,Cotran RS.Cytokines and endothelial cell biology.Physiol Rev 1990;70:427-51.
5.Zlotnik A et al.Immunity,2000,12;121-127.
6.Fernandez EJ,Lolis E.Structure,function,and inhibition of chemokines J.Annu Rev Pharmacol Toxicol,2002,42:469-499.
7.Luo J,Luo Z,Zhou N,et al.Attachment of C-terminus of SDF-1 enhances the biological activity of its N-terminal peptide J.Bioch Biophy Res Communicat,1999,264(1):42-47.
8.Amara A,Lorthioir O,Valenzuela A,et al.SDF-1 asso- ciates with heparin sulfates through the first β-strand of the chemokine J.J Bio Chem,1999,274(34):23916-23 925.
9.黄仕和,许四宏.趋化因子及其未来.生命的化学.2001,21(4):335.
10.Urphy P et al.Pharmacological Reviews,2000,52(1);145-176.
11.Baggiolini M.Chemokines and leucocyte traffic.Nature,1998,392(6676);565-568.
12.Murdoch C,Finn A.Chemokine receptors and their role in inflammation and infectious diseases J.Blood,2000,95(10):3032-3043.
13.王健,赵金红.趋化因子受体研究进展.现代预防医学.2006,33(2):165.
14.Douglas GC,Thirkill TL et al.Chemokine receptor expression by human syncytiotrophoblast.Immunol J.2001 Feb;49(2):97-114.
15.Ishii M,Hayakawa S et al.Expression of functional chemokine receptors of human placental cells.Immunol J.2000 Dec;44(6):365-73.
16.Bustamante S,Garrido H et al.CXCR-4 and CCR-5 expression in normal term human placenta.Invest Clin.2005 Mar;46(1):25-35.
17. Wu,Li DJ et al. The expression of CXCR4/CXCL12 u Xin first-trimester human trophoblast cells.Biol Reprod. 2004 Jun;70(6): 1877-85.
18. Hannan NJ, Jones RL et al. The chemokines, CX3CL1, CCL14, and CCL4, promote human trophoblast migration at the feto-maternal interface.Biol Reprod. 2006 May;74(5): 896-904.
19. Richard Horuk.Chemokine receptors J.Cytokine Growth Factor Rev, 2001,12(14):313-335.
20. Murdoch C, Finn A.Chemokine receptors and their role in inflammation and infectious diseases J.Blood,2000,95 (10):3032-3043.
21. Engert S,Rieger L et al. Profiling chemokines, cytokines and growth factors in human early pregnancy decidua by protein array. Immunol J. 2007 Aug;58(2): 129-37.
22. Fernandez-Botran R, Chilton PM, Ma Y. Soluble cytokine receptors: their roles in immunoregulation, disease, and therapy. Adv Immunol, 1996; 63: 269-336.
23. Jonsson Y, et al. Cytokine mapping of sera from women with preeclampsia and normal pregnancies.J Reprod Immunol. 2006 Jun;70(1-2):83-91.
24. Tuomisto T, et al. Tumor suppressor and growth regulatory genes are overexpressed in severe early-onset preeclampsia--an array study on case-specific human preeclamptic placental tissue.Acta Obstet Gynecol Scand. 2005 Jul;84(7):679-89.
25. Brewster JA,et al.Host inflammatory response profiling in preeclampsia using an in vitro whole blood stimulation model.Hypertens Pregnancy. 2008;27(1):1-16.
26. Katabuchi H, et al. Characterization of macrophages in the decidual atherotic spiral artery with special reference to the cytology of foam cells. Med Electron Microsc. 2003 Dec;36(4):253-62.
27. Lockwood CJ, et al. Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha and interleukin-1 beta in first trimester human decidual cells: implications for preeclampsia.Am J Pathol. 2006 Feb;168(2):445-52.
28. Huang SJ,Schatz F et al. Regulation of chemokine production in response to pro-inflammatory cytokines in first trimester decidual cells. Immunol J.2006 Dec;72 (1-2):60-73.
29. Hoist RM,Laurini R et al. Expression of cytokines and chemokines in cervical and amniotic fluid: relationship to histological chorioamnionitis. Matern Fetal Med J. 007 Dec;20(12):885-93.
30. Esplin MS,Peltier MR et al. Monocyte chemotactic protein-1 expression is increased in human gestational tissues during term and preterm labor.Placenta. 2005 Sep-Oct;26(8-9):661-71.
31. Huang Y,Zhu XY et al. Chemokine CXCL16, a scavenger receptor, induces proliferation and invasion of first-trimester human trophoblast cells in an autocrine manner.Hum Reprod. 2006 Apr;21(4): 1083-91.
32. He YY,Du MR et al. Regulation of C-C motif chemokine ligand 2 and its receptor in human decidual stromal cells by pregnancy-associated hormones in early gestation.Hum Reprod. 2007 Oct;22(10):2733-42.
33. Hirota Y,Osuga Y et al. The expression and possible roles of chemokine CXCL11 and its receptor CXCR3 in the human endometrium. Immunol J. 2006 Dec 15;177(12):8813-21.
34. Borroni EM, Buracchi C et al. The chemoattractant decoy receptor D6 as a negative regulator of inflammatory responses.Biochem Soc Trans. 2006 Dec;34(Pt6):1014-7.
35. Borroni EM, Buracchi C et al. Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6.Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2319-24.
2.Trudinger BJ,Giles WB,Cook CM,Bombardieri J,Collins L.Fetal umbilical artery flow velocity waveforms and placental resistance:Clinical significance.Br J Obstet Gynaecol 1985,92:23-30.
3.Wang X,Athayde N,Trudinger B.Placental vascular disease-A proinflammatory response of innate immunity.An J Obstet Gynecol 2003;189(6 suppl):S125.
4.Wang X,Athayde N,Trudinger B.Expression of toll-like receptor 4 in human endothelial cells stimulated by fetal plasma with umbilical placental vascular disease.J Soc Gynecol Investig 2003;10(2 suppl):#659.
5.Trudinger B,Wang J,Athayde N,Beutler L,Wang X.Association of umbilical placental vascular disease with fetal acute inflammatory cytokine responses.J Soc Gynecol Investig 2002;9:152-7.
6.Pober JS,Cotran RS.Cytokines and endothelial cell biology.Physiol Rev 1990;70:427-51.
7.Wang X,Athayde N,Trudinger B.Microvascular endothelial cell activation is present in the umbilical placental microcirculation in fetal placental vascular disease.Am J Obstet Gynecol 2004 Mar;190(3):596-601.
8.Hwang J,Kim CW,et al.Angiogenic activity of human CC chemokine CCL15 in vitro and in vivo.FEBS Lett.2004,570(1-3):47-51.
9.乐杰.妇产科学[M].第4版.北京:人民卫生出版社,1996:138-140.
10.莫娥清,刘穗玲.94例妊高征及其并发症分析.中国实用妇科与产科杂志.1996,12:215—216.
11.Fernandez-Botran R,Chilton PM,Ma Y.Soluble cytokine receptors:their roles in immunoregulation,disease,and therapy.Adv Immunol,1996;63:269-336.
12.Jonsson Y,et al.Cytokine mapping of sera from women with preeclampsia and normal pregnancies.J Reprod Immunol.2006 Jun;70(1-2):83-91.
13.Tuomisto T,et al.Tumor suppressor and growth regulatory genes are overexpressed in severe early-onset preeclampsia--an array study on case-specific human preeclamptic placental tissue.Acta Obstet Gynecol Scand.2005 Jul;84(7):679-89.
14.Brewster JA,et al.Host inflammatory response profiling in preeclampsia using an in vitro whole blood stimulation model.Hypertens Pregnancy.2008;27(1):1-16.
15.Katabuchi H,et al.Characterization of macrophages in the decidual atherotic spiral artery with special reference to the cytology of foam cells.Med Electron Microsc.2003 Dec;36(4):253-62.
16.Lockwood CJ,et al.Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha and interleukin-lbeta in first trimester human decidual cells:implications for preeclampsia.Am J Pathol.2006Feb;168(2):445-52.
17.李翠兰等.重度妊娠高血压综合征患者子宫胎盘病理变化及其临床意义.中华妇产科杂志.2000,11:651.
18.Esther L,Birgit F,et al.Gene Profiling in Atherosclerosis Reveals a Key Role for Small Inducible Cytokines.Circulation.2005,111:3443-34.
19.Rina Yu,Chu-Sook Kim,et al.Involvement of leukotactin-1,a novel CC chemokine,in human atherosclerosis.Athrosclerosis.2004,174:35-42.
20.Won-Ha Lee,Se-Hwa Kim,et al.A novel chemokine,Leukotactin-1,induces chemotaxis,pro-atherogenic cytokines,and tissue factor expression in atherosclerosis.Atherosclerosis.2002,161:255-260.
21.Zlotnik A,et al.Immunity,2000,12:121-127.
22.Youn BS,Zhang SM,Lee EK,et al.Molecular cloning of leukotactin-1:a novel human beta-chemokine,a chemoa- ttractant for neutrophils,monocytes,and lymphocytes,and a potent agonist at CC chemokine recetpors 1 and 3.J Immunol,1997,159(11):5201.
23.Youn BS,Zhang SM,Broxmeyer HE,et al.Characterization of Ckbeta8 and Ckbeta8-1:two alternatively spliced forms of human beta-chemokine,chemoattractants for neutrophils,monocytes,and lynphocytes,and potent agonists at CC chemokine receptor 1.Blood,1998,91(9):3118.
24.Lee JK,Lee EH,Yun YP,et al.Truncation of NH2-terminal Amino Acid Residues Increases Agonistic Potency of Leukotactin-1 on CC.Chemokine Receptors 1 and 3.J Biol Chem,2002,277(17):14757.
25.Zhang SM,Youn BS,Gao JL,et al.Differential Effects of Leukotactin-1 and Macrophage Inflammatory Protein-1αon Neutrophils Mediated by CCR1.J Immunol,1999,162(8):4938.
26.Ko J,Kim IS,et al.Leukotactin-1/CCL15-induced chemotaxis signaling through CCR1 in HOS cells.FEBS Lett.2002,515(1-3):159-64.
27.Lee WH,Kim SH,Jeong EM,et al.A novel chemokine,Leukotactin-1,induces chemotaxis,pro-atherogenic cytokines,and tissue factor expression in atherosclerosis.Atherosclerosis,2002,161(2):255-60.
28.Richard Horuk.Chemokine receptors J.Cytokine Growth Factor Rev,2001,12(14):313-335.
29.Murdoch C,Finn A.Chemokine receptors and their role in inflammation and infectious diseases J.Blood,2000,95(10):3032-3043.
30.王健,赵金红.趋化因子受体研究进展.现代预防医学.2006,33(2):165.
31.James D,Frank M.Chemokine receptors A brief overview.Clinical and Applied Immunology Reviews.2000,1:105-125.
32.Sheikine Y,Hansson GK.Chemokines and atherosclerosis.Ann Med.2004,36(2):98-108.
33.Potteaux S,Combadière C,et al.Chemokine Receptor CCR1 Disruption in Bone Marrow Cells Enhances Atherosclerotic Lesion Development and Inflammation in Mice.Mol Med.2005,11(1-12):16-20.
1.Wang X,Athayde N,Trudinger B.Placental vascular disease-A proinflammatory response of innate immunity.An J Obstet Gynecol 2003;189(6 suppl):S125.
2.Wang X,Athayde N,Trudinger B.Expression of toll-like receptor 4 in human endothelial cells stimulated by fetal plasma with umbilical placental vascular disease.J Soc Gynecol Investig 2003;10(2 suppl):#659.
3.Trudinger B,Wang J,Athayde N,Beutler L,Wang X.Association of umbilical placental vascular disease with fetal acute inflammatory cytokine responses.J Soc Gynecol Investig 2002;9:152-7.
4.Pober JS,Cotran RS.Cytokines and endothelial cell biology.Physiol Rev 1990;70:427-51.
5.Zlotnik A et al.Immunity,2000,12;121-127.
6.Fernandez EJ,Lolis E.Structure,function,and inhibition of chemokines J.Annu Rev Pharmacol Toxicol,2002,42:469-499.
7.Luo J,Luo Z,Zhou N,et al.Attachment of C-terminus of SDF-1 enhances the biological activity of its N-terminal peptide J.Bioch Biophy Res Communicat,1999,264(1):42-47.
8.Amara A,Lorthioir O,Valenzuela A,et al.SDF-1 asso- ciates with heparin sulfates through the first β-strand of the chemokine J.J Bio Chem,1999,274(34):23916-23 925.
9.黄仕和,许四宏.趋化因子及其未来.生命的化学.2001,21(4):335.
10.Urphy P et al.Pharmacological Reviews,2000,52(1);145-176.
11.Baggiolini M.Chemokines and leucocyte traffic.Nature,1998,392(6676);565-568.
12.Murdoch C,Finn A.Chemokine receptors and their role in inflammation and infectious diseases J.Blood,2000,95(10):3032-3043.
13.王健,赵金红.趋化因子受体研究进展.现代预防医学.2006,33(2):165.
14.Douglas GC,Thirkill TL et al.Chemokine receptor expression by human syncytiotrophoblast.Immunol J.2001 Feb;49(2):97-114.
15.Ishii M,Hayakawa S et al.Expression of functional chemokine receptors of human placental cells.Immunol J.2000 Dec;44(6):365-73.
16.Bustamante S,Garrido H et al.CXCR-4 and CCR-5 expression in normal term human placenta.Invest Clin.2005 Mar;46(1):25-35.
17. Wu,Li DJ et al. The expression of CXCR4/CXCL12 u Xin first-trimester human trophoblast cells.Biol Reprod. 2004 Jun;70(6): 1877-85.
18. Hannan NJ, Jones RL et al. The chemokines, CX3CL1, CCL14, and CCL4, promote human trophoblast migration at the feto-maternal interface.Biol Reprod. 2006 May;74(5): 896-904.
19. Richard Horuk.Chemokine receptors J.Cytokine Growth Factor Rev, 2001,12(14):313-335.
20. Murdoch C, Finn A.Chemokine receptors and their role in inflammation and infectious diseases J.Blood,2000,95 (10):3032-3043.
21. Engert S,Rieger L et al. Profiling chemokines, cytokines and growth factors in human early pregnancy decidua by protein array. Immunol J. 2007 Aug;58(2): 129-37.
22. Fernandez-Botran R, Chilton PM, Ma Y. Soluble cytokine receptors: their roles in immunoregulation, disease, and therapy. Adv Immunol, 1996; 63: 269-336.
23. Jonsson Y, et al. Cytokine mapping of sera from women with preeclampsia and normal pregnancies.J Reprod Immunol. 2006 Jun;70(1-2):83-91.
24. Tuomisto T, et al. Tumor suppressor and growth regulatory genes are overexpressed in severe early-onset preeclampsia--an array study on case-specific human preeclamptic placental tissue.Acta Obstet Gynecol Scand. 2005 Jul;84(7):679-89.
25. Brewster JA,et al.Host inflammatory response profiling in preeclampsia using an in vitro whole blood stimulation model.Hypertens Pregnancy. 2008;27(1):1-16.
26. Katabuchi H, et al. Characterization of macrophages in the decidual atherotic spiral artery with special reference to the cytology of foam cells. Med Electron Microsc. 2003 Dec;36(4):253-62.
27. Lockwood CJ, et al. Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha and interleukin-1 beta in first trimester human decidual cells: implications for preeclampsia.Am J Pathol. 2006 Feb;168(2):445-52.
28. Huang SJ,Schatz F et al. Regulation of chemokine production in response to pro-inflammatory cytokines in first trimester decidual cells. Immunol J.2006 Dec;72 (1-2):60-73.
29. Hoist RM,Laurini R et al. Expression of cytokines and chemokines in cervical and amniotic fluid: relationship to histological chorioamnionitis. Matern Fetal Med J. 007 Dec;20(12):885-93.
30. Esplin MS,Peltier MR et al. Monocyte chemotactic protein-1 expression is increased in human gestational tissues during term and preterm labor.Placenta. 2005 Sep-Oct;26(8-9):661-71.
31. Huang Y,Zhu XY et al. Chemokine CXCL16, a scavenger receptor, induces proliferation and invasion of first-trimester human trophoblast cells in an autocrine manner.Hum Reprod. 2006 Apr;21(4): 1083-91.
32. He YY,Du MR et al. Regulation of C-C motif chemokine ligand 2 and its receptor in human decidual stromal cells by pregnancy-associated hormones in early gestation.Hum Reprod. 2007 Oct;22(10):2733-42.
33. Hirota Y,Osuga Y et al. The expression and possible roles of chemokine CXCL11 and its receptor CXCR3 in the human endometrium. Immunol J. 2006 Dec 15;177(12):8813-21.
34. Borroni EM, Buracchi C et al. The chemoattractant decoy receptor D6 as a negative regulator of inflammatory responses.Biochem Soc Trans. 2006 Dec;34(Pt6):1014-7.
35. Borroni EM, Buracchi C et al. Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6.Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2319-24.