Wykretowicz A, Issekutz T B
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
J Mol Cell Cardiol. 1993 Apr;25(4):469-75. doi: 10.1006/jmcc.1993.1052.
Lymphocyte migration out of the blood to inflammatory sites is preceded by the adherence of lymphocytes to the vascular endothelium. This lymphocyte binding is enhanced by cytokine activation of the endothelial cells (EC). Small peritoneal exudate lymphocytes (sPEL) migrate preferentially into cutaneous inflammation and to skin injected with INF gamma, TNF alpha or LPS. These cells adhere also to rat microvascular EC and this adherence correlates well with migratory properties of sPEL. Lymphocyte EC adhesion is in part mediated by the VLA-4 molecule on the lymphocytes. Since differences between microvascular and large vessel EC have been described, we investigated whether sPEL adherence to both types of EC is governed by similar molecular mechanisms. Lymphocyte adhesion was low to unstimulated microvascular EC and augmented by pretreatment of EC with INF gamma, TNF alpha and LPS. In contrast, lymphocyte adhesion to unstimulated large vessel (aortic) EC was higher than to microvascular EC and could not be increased by cytokine or LPS treatment. Anti VLA-4 mAb inhibited the enhanced cytokine stimulated adhesion to microvascular EC without affecting adhesion of sPEL to unstimulated EC. Anti VLA-4 mAb inhibited the high spontaneous adhesion to aortic EC, suggesting that with both EC, adhesion is in part VLA-4 dependent.
淋巴细胞从血液迁移至炎症部位之前，淋巴细胞会先黏附于血管内皮。内皮细胞（EC）的细胞因子激活可增强这种淋巴细胞结合。小腹腔渗出淋巴细胞（sPEL）优先迁移至皮肤炎症部位以及注射了INFγ、TNFα或LPS的皮肤。这些细胞也黏附于大鼠微血管EC，且这种黏附与sPEL的迁移特性密切相关。淋巴细胞与EC的黏附部分由淋巴细胞上的VLA-4分子介导。由于已描述了微血管EC和大血管EC之间的差异，我们研究了sPEL对这两种类型EC的黏附是否受相似分子机制的调控。淋巴细胞对未刺激的微血管EC的黏附较低，而用INFγ、TNFα和LPS预处理EC可增强这种黏附。相比之下，淋巴细胞对未刺激的大血管（主动脉）EC的黏附高于对微血管EC的黏附，且细胞因子或LPS处理无法增加这种黏附。抗VLA-4单克隆抗体抑制了细胞因子刺激增强的对微血管EC的黏附，而不影响sPEL对未刺激EC的黏附。抗VLA-4单克隆抗体抑制了对主动脉EC的高自发黏附，表明对于这两种EC，黏附部分依赖于VLA-4。
