摘要
目的川崎病(Kawasaki Disease,KD)大部分病人血清中存在抗内皮细胞受体抗体-IgM(IgM An-ti-endothelial cell antibodies,IgM-AECA)。该研究旨在探讨抗内皮细胞受体抗体(AECA)通过何种途径诱导内皮细胞细胞内吸附分子-1(intercellular adhesion molecule-1,ICAM-1)的表达以激活血管内皮细胞。方法检测30名KD患儿血清IgM-AECA浓度,并从17名AECA阳性KD患儿血清中提纯IgM-AECA,用IgM-AECA直接刺激人冠状动脉内皮细胞(human coronary artery endothelial cells,HCAEC)后,通过R T-PCR及ELISA方法检测ICAM-1 mR NA及蛋白的表达,同时应用了PD98059,SB203580,dimethylaminopurine(DMAP)和parthenolide,4种蛋白激酶阻断剂观察IgM-AECA通过何种途径激活HCAEC。结果 KD病人血清中的IgM-AECA可使HCAEC的ICAM-1 mRNA及蛋白表达明显增加,SB203580(p38阻断剂)、DMAP(JNK阻断剂)及parthenolide(NF-κB阻断剂)明显抑制ICAM-1的表达(均P<0.01),而PD98059(ERK1/2阻断剂)不能抑制ICAM-1的表达(P>0.05)。结论 KD病人血清中的IgM-AECA通过增强ICAM-1的表达来激活内皮细胞,IgM-AECA通过p38、JNK MAPK及NF-κB通路诱导ICAM-1的表达,IgM-AECA可能在KD冠状动脉病变的发生中发挥重要作用。
【Objective】 IgM Anti-endothelial cell antibodies（IgM-AECA） were found among many patients with KD.The aim of this study was to investigate the signal transduction pathways of AECA induced intercellular adhesion molecule-1（ICAM-1） expression.【Methods】 Serum IgM-AECE concentrations were measured in 30 KD patients.IgM-AECA were purified by gel filtration from the sera of 17 AECE positive KD patients,and their ability to induce ICAM-1 mRNA and protein expressions of human coronary artery endothelial cells（HCAEC） were evaluated by RT-PCR analysis and ELISA.To address the signal transduction pathways involved in IgM-AECA induced ICAM-1 expression,the blocking effect of four protein kinase inhibitors,PD98059,SB203580,dimethylaminopurine（DMAP） and parthenolide were measured.【Results】 IgM-AECA from KD patients induced ICAM-1 mRNA and protein expression of HCAEC significantly.The upregulation of ICAM-1 expression was significantly inhibited by SB203580,DMAP and parthenolide,but not by PD98059.【Conclusions】 IgM-AECA in KD sera were able to activate endothelial cells by upregulation of ICAM-1 expression,possibly via p38,JNK MAPK and NF-κB signal transduction pathways.Thus,IgM-AECA may play a pathogenic role in the development of coronary arterial lesions in KD.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2012年第4期34-39,共6页
China Journal of Modern Medicine
基金
大连市卫生局(No:2010-153)
