CD226 mediates platelet and megakaryocytic cell adhesion to vascular endothelial cells
CD226 mediates platelet and megakaryocytic cell adhesion to vascular endothelial cells
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DOI：
10.1074/jbc.m300702200
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发表时间：
2003-09-19
影响因子：
4.8
通讯作者：
Shibuya, A
中科院分区：
文献类型：
--
作者：
Kojima, H;Kanada, H;Shibuya, A
血小板粘附血管内皮细胞是一种病理生理相关的细胞间相互作用。然而，这种细胞相互作用的机制尚不完全清楚。为了寻找CD226粘附分子在血小板上表达的配体，我们发现人脐静脉内皮细胞（HUVEC）表达了大量的CD226配体。我们证明了凝血酶激活的血小板与完整的HUVEC结合，而不是静止的血小板。抗CD226单克隆抗体特异性抑制这种结合，表明CD226介导凝血酶活化血小板与HUVEC的细胞间结合。我们还证明凝血酶激活血小板可诱导CD226的酪氨酸磷酸化以及CD226介导的血小板粘附。此外，利用突变体转染的实验表明，CD226残基322处的酪氨酸对其粘附功能起重要作用。CD226在原代巨核细胞和巨核细胞系中也有表达。抗cd226单克隆抗体抑制巨核细胞系与HUVEC的结合。综上所述，这些结果揭示了血小板和巨核细胞粘附血管内皮细胞的新机制。
Platelet adhesion to vascular endothelial cells is a pathophysiologically relevant cell-to-cell interaction. However, the mechanisms underlying this cellular interaction are incompletely understood. In search of the ligand for CD226 adhesion molecule expressed on platelets, we found that human umbilical vein endothelial cells (HUVEC) express significant amount of putative CD226 ligand. We demonstrated that thrombin-activated, but not resting, platelets bind to intact HUVEC. Anti-CD226 monoclonal antibody specifically inhibited the binding, indicating that CD226 mediates the intercellular binding between thrombin-activated platelets and HUVEC. We also demonstrated that platelet activation with thrombin induces tyrosine phosphorylation of CD226 as well as CD226-mediated platelet adhesion. Moreover, experiments using mutant transfectants suggested that the tyrosine at residue 322 of CD226 plays an important role for its adhesive function. CD226 was also expressed on primary megakaryocytes and megakaryocytic cell lines. Anti-CD226 monoclonal antibody inhibited binding of megakaryocytic cell lines to HUVEC. Taken together, these results reveal a novel mechanism for adhesion of platelets and megakaryocytic cells to vascular endothelial cells.