细胞因子对心脏微血管内皮细胞与淋巴细胞粘附的影响

Lymphocyte adherence to rat heart microvascular endothelial cells by cytokines

目的：观察细胞因子对心脏微血管内皮细胞表面细胞间粘附分子－１（ｉｎｔｅｒｃｅｌｕｌａｒａｄｈｅｓｉｏｎｍｏｌｅｃｕｌｅ－１，ＩＣＡＭ－１）的表达的调控，及对内皮细胞与激活淋巴细胞粘附的影响。方法：体外培养大鼠心脏微血管内皮细胞，以肿瘤坏死因子（ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒ－α，ＴＮＦ－α）、白细胞介素－６（ｉｎｔｅｒｌｅｕｋｉｎ６，ＩＬ－６）和白细胞介素－１（ｉｎｔｅｒｌｅｕｋｉｎ１β，ＩＬ－１β）诱导。采用免疫组织化学染色法观察内皮细胞表面ＩＣＡＭ－１表达；采用粘附试验和抗ＩＣＡＭ－１或抗ＬＦＡ－１单克隆抗体阻断抑制试验。结果：ＴＮＦ－α、ＩＬ－６和ＩＬ－１β诱导内皮细胞１８～２４ｈ，均可使内皮细胞与淋巴细胞的粘附率显著增加，ＴＮＦ－α和ＩＬ－１β的诱导还可使内皮细胞表面ＩＣＡＭ－１分子表达明显增强，表现为ＩＣＡＭ－１表达阳性细胞数增多，着色加深。用１０～２０ｍｇ／Ｌ抗ＩＣＡＭ－１或抗ＬＦＡ－１单克隆抗体均可部分抑制内皮细胞与淋巴细胞的粘附。结论：ＴＮＦ－α和ＩＬ－１β可以有效地激活心脏微血管内皮细胞，通过诱导内皮细胞ＩＣＡＭ－１表达增多。

Abstract AIM:Induction expression of intercellular adhession molecule-1 (ICAM-1) on heart microvascular endothelial cells(HMEC) and adhesion of lymphocytes to endothelial cells may be a critical step in cardiac injury associated with immunopathology.We investigated the involvement of cytokines on lymphocytes-HMEC adhesion,and on induction of ICAM-1 in HMEC.METHODS:Cultured rat HMEC stimulated by TNF-α、IL-6 and IL-1β.ICAM-1 expression on cultured HMEC was determined through immunohistochemical analysis.Actived lymphocyte-HMEC adhesion was observed by adherence assay and by anti-ICAM-1 mono clonal antibody or anti-LFA-1 (leukocyte function associate antigen-1) monoclonal antibody inhibition assay.RESULTS:Lymphocyte-endothelial cell adhesion was markedly increased after endothelial cell stimulated by TNF-α、IL-6 and IL-1β for 18～24h ICAM-1 molecule expression on endothelial cells was significantly stimulated by TNF-α and IL-1β.The stimulatory effect of TNF-α on lymphocyte-endothelial cell adhesion was partially inhibited by 11%～45 3% in the presence of the anti-ICAM-1 or anti-LFA-1 monloclonal antibodies(10～20 mg/L) CONCLUSION:TNF-α and IL-1β might promoted lymphocyte-endothelial cell adhesion through ICAM-1 expression,however,anti-ICAM-1 or anti-LFA-1 monoclonal antibodies could effectively block this adhesion process. MeSH Endothelium;Cells; Lymphocytes ;Cytokines