C5A-INDUCED EXPRESSION OF P-SELECTIN IN ENDOTHELIAL-CELLS
C5A-INDUCED EXPRESSION OF P-SELECTIN IN ENDOTHELIAL-CELLS
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DOI：
10.1172/jci117430
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发表时间：
1994-09-01
影响因子：
15.9
通讯作者：
WARD, PA
中科院分区：
文献类型：
--
作者：
FOREMAN, KE;VAPORCIYAN, AA;WARD, PA
人脐静脉内皮细胞最近已被证明对C5 a有反应，细胞内Ca 2+增加，D-肌肌醇1，4，5-三磷酸的产生和超氧阴离子的产生。在目前的研究中，已经发现C5 a以时间和剂量依赖性的方式引起内皮P-选择素的快速表达、血管性血友病因子的分泌和人中性粒细胞的增殖。C5 a对中性粒细胞P-选择素表达和粘附的影响与组胺和凝血酶对内皮细胞的影响相似。C5 a刺激的内皮细胞对中性粒细胞的抑制作用被抗P-选择素阻断，但不被细胞间粘附分子1、E-选择素或CD 18抗体阻断。基于细胞的ELISA技术已经证实了暴露于C5 a的内皮细胞中P-选择素的上调。已证实C5 a与内皮细胞的结合，结合的分子类似于与嗜中性粒细胞结合的分子的10%。通过逆转录酶-PCR技术，已经显示内皮细胞含有C5 a受体的mRNA。这些数据表明，C5 a可能是一个重要的炎症介质之间的早期粘附相互作用的中性粒细胞和内皮细胞在急性炎症反应。
Human umbilical vein endothelial cells have recently been shown to respond to C5a with increases in intracellular Ca2+, production of D-myo-inositol 1,4,5-triphosphate and superoxide anion generation. In the current studies, C5a has been found to cause in a time- and dose-dependent manner rapid expression of endothelial P-selectin, secretion of von Willebrand factor, and adhesiveness for human neutrophils. The effects of C5a in P-selectin expression and adhesiveness of neutrophils were similar to the effects of histamine and thrombin on endothelial cells. The adhesiveness of C5a-stimulated endothelium for neutrophils was blocked by anti-P-selectin, but not by antibodies to intercellular adhesion molecule 1, E-selectin, or CD18. A cell-based ELISA technique has confirmed upregulation of P-selectin in endothelial cells exposed to C5a. Binding of C5a to endothelial cells has been demonstrated, with molecules bound being similar to 10% of those binding to neutrophils. By a reverse transcriptase-PCR technique, endothelial cells have been shown to contain mRNA for the C5a receptor. These data suggest that C5a may be an important inflammatory mediator for the early adhesive interactions between neutrophils and endothelial cells in the acute inflammatory response.