Kuijper P H, Gallardo Torres H I, Lammers J W, Sixma J J, Koenderman L, Zwaginga J J
Department of Haematology, University Hospital Utrecht, The Netherlands.
Blood. 1997 Jan 1;89(1):166-75.
At sites of vessel wall damage, the primary hemostatic reaction involves platelet and fibrin deposition. At these sites, circulating leukocytes marginate and become activated. Adhered platelets can support leukocyte localization; however, the role of fibrin in this respect is not known. We studied the adhesion of human neutrophils (polymorphonuclear leukocytes [PMNs]) to endothelial extracellular matrix (ECM)-bound fibrin and platelets under flow conditions. ECM alone did not show PMN adhesion. ECM-coated cover slips were perfused with plasma to form a surface-bound fibrin network, and/or with whole blood to allow platelet adhesion. Unstimulated PMNs adhered to fibrin at moderate shear stress (20 to 200 mPa). ECM-bound platelets induced rolling adhesion and allowed more PMNs to adhere at higher shear (320 mPa). ECM coated with both platelets and fibrin induced more static and shear-resistant PMN adhesion. PMN adhesion to fibrin alone but not to platelet/fibrin surfaces was inhibited by soluble fibrinogen. Adhesion to fibrin alone was inhibited by CD11b and CD18 blocking antibodies. Furthermore, fibrin formed under flow conditions showed up to threefold higher PMN adhesion compared with fibrin formed under static conditions, due to structural differences. These results indicate that circulating PMNs adhere to fibrin in an integrin-dependent manner at moderate shear stresses. However, at higher shear rates (> 200 mPa), additional mechanisms (ie, activated platelets) are necessary for an interaction of PMNs with a fibrin network.
在血管壁损伤部位，初级止血反应涉及血小板和纤维蛋白沉积。在这些部位，循环中的白细胞靠边并被激活。黏附的血小板可支持白细胞定位；然而，纤维蛋白在这方面的作用尚不清楚。我们研究了在流动条件下人中性粒细胞（多形核白细胞[PMN]）与内皮细胞外基质（ECM）结合的纤维蛋白和血小板的黏附情况。单独的ECM未显示出PMN黏附。用血浆灌注涂有ECM的盖玻片以形成表面结合的纤维蛋白网络，和/或用全血以允许血小板黏附。未刺激的PMN在中等剪切应力（20至200 mPa）下黏附于纤维蛋白。ECM结合的血小板诱导滚动黏附，并使更多PMN在较高剪切力（320 mPa）下黏附。同时涂有血小板和纤维蛋白的ECM诱导更多的静态和抗剪切PMN黏附。可溶性纤维蛋白原抑制PMN单独与纤维蛋白的黏附，但不抑制与血小板/纤维蛋白表面的黏附。单独与纤维蛋白的黏附被CD11b和CD18阻断抗体抑制。此外，由于结构差异，流动条件下形成的纤维蛋白与静态条件下形成的纤维蛋白相比，显示出高达三倍的PMN黏附。这些结果表明，循环中的PMN在中等剪切应力下以整合素依赖性方式黏附于纤维蛋白。然而，在较高剪切速率（>200 mPa）下，PMN与纤维蛋白网络相互作用还需要其他机制（即活化的血小板）。
