Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the α2β1-integrin receptor
Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the α2β1-integrin receptor
复制标题
DOI：
10.1182/blood-2006-08-039925
复制
发表时间：
2007-05-01
期刊：
影响因子：
20.3
通讯作者：
Iozzo, Renato V.
中科院分区：
文献类型：
--
作者：
Bix, Gregory;Iozzo, Rex A.;Iozzo, Renato V.
内排斥素是血管基底膜蛋白多糖的C末端片段，通过α2β1整合素受体抑制血管生成。由于这种整合素也与血小板-胶原反应有关，而且内层蛋白或其片段是在损伤和炎症反应中产生的，我们假设内层蛋白也可能影响血小板的生物学。我们发现，内皮膜蛋白支持依赖于α2β1的血小板黏附，而不明显地激活或聚集血小板。值得注意的是，内胚层蛋白以src激酶依赖的方式增强了血小板中的胶原诱导的反应，并增强了α2β1整合素功能阻断抗体的胶原抑制效应。综上所述，这些结果表明，内皮层蛋白/α2β1整合素的相互作用和作用是特异的，依赖于细胞类型，不同于胶原蛋白暴露所产生的作用，可能是由于细胞在α2β1整合素激活/配体亲和状态上的差异。这些研究还表明，血管抑制基底膜片段在血小板生物学中的作用到目前为止尚未被认识到。(C)2007年由美国血液病学会公布。
Endorepellin, a C-terminal fragment of the vascular basement membrane proteoglycan perlecan, inhibits angiogenesis via the alpha 2 beta 1-integrin receptor. Because this integrin is also implicated in platelet-collagen responses and because endorepellin or its fragments are generated in response to injury and inflammation, we hypothesized that endorepellin could also affect platelet biology. We discovered that endorepellin supported alpha 2 beta 1-dependent platelet adhesion, without appreciably activating or aggregating platelets. Notably, endorepellin enhanced collagen-evoked responses in platelets, in a src kinase-dependent fashion, and enhanced the collagen-inhibitory effect of an alpha 2 beta 1-integrin function-blocking antibody. Collectively, these results suggest that endorepellin/alpha 2 beta 1-integrin interaction and effects are specific and dependent on cell type, differ from those emanated by exposure to collagen, and may be due to cellular differences in alpha 2 beta 1-integrin activation/ligand affinity state. These studies also suggest a heretofore unrecognized role for angiostatic basement membrane fragments in platelet biology. (C) 2007 by The American Society of Hematology.