Neutrophil enhancement of fibrin deposition under flow through platelet-dependent and-independent mechanisms
Neutrophil enhancement of fibrin deposition under flow through platelet-dependent and-independent mechanisms
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DOI：
10.1161/hq1201.100255
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发表时间：
2001-12-01
影响因子：
8.7
通讯作者：
Diamond, SL
中科院分区：
文献类型：
--
作者：
Goel, MS;Diamond, SL
我们研究了在层流条件下附着的中性粒细胞对纤维蛋白沉积的影响。在静脉壁剪切速率为62.5 s（-1）的情况下，将柠檬酸重钙化无血小板血浆（PFP）灌注于粘附在纤维蛋白原包覆玻璃上的中性粒细胞上15分钟，导致每个中性粒细胞周围有密集的纤维蛋白沉积，而单独在玻璃上的纤维蛋白沉积较少。抗cd18或抗cd11b或更高的剪切速率（250 s(-1)）可显著减少中性粒细胞上的纤维蛋白沉积。明显较少的纤维蛋白沉积在粘附的纤维蛋白原包被珠周围，这表明非特异性的“横截面捕获”效应不是中性粒细胞上大量纤维蛋白沉积的原因。直接观察中性粒细胞捕获纤维蛋白的情况，以及XIIa因子抑制剂（50 mug/mL玉米胰蛋白酶抑制剂[CTI]）或弹性酶/组织蛋白酶G抑制剂（methoxysuccinyl - ala - ala - pro- ala -氯甲基酮/ z - gly - leu - ph - cmk， 100 mu mol/L）在15分钟内消除纤维蛋白沉积的情况，表明中性粒细胞可以捕获在缺乏CTI的重钙化PFP中流动的短纤维蛋白链，还可以通过XIIa因子抑制剂减弱的途径促进凝血酶的生成。当中性粒细胞与纤维蛋白原表面的血小板相互作用时，在灌注复钙化的cgi处理的PFP之前，与单独包裹血小板或单独包裹中性粒细胞表面的纤维蛋白沉积相比，与粘附在胶原蛋白上的血小板形成的纤维蛋白沉积相比，观察到纤维蛋白沉积明显。中性粒细胞对血小板介导的纤维蛋白形成的促进作用被弹性蛋白酶或组织蛋白酶G抑制剂减弱，但抗组织因子抗体不减弱。中性粒细胞可以通过释放的蛋白酶与血小板相互作用，在静脉血栓形成或炎症的低流量条件下，增加cgi处理过的血浆中血小板促凝活性和纤维蛋白的形成。
We examined the effect of adherent neutrophils on fibrin deposition under laminar flow conditions. Perfusion of recalcified citrated platelet-free plasma (PFP) over neutrophils adherent to fibrinogen-coated glass at a venous wall shear rate of 62.5 s(-1) for 15 minutes resulted in dense deposition of fibrin around each neutrophil, whereas fibrin deposition on glass alone was sparse. Fibrin deposition on neutrophils was markedly reduced by anti-CD18 or anti-CD11b or a higher shear rate (250 s(-1)). Significantly less fibrin was deposited around adherent fibrinogen-coated beads, indicating that nonspecific "cross-sectional capture" effects were not responsible for the massive fibrin deposition on neutrophils. Direct visualization of fibrin capture by neutrophils and elimination of fibrin deposition at 15 minutes by a factor XIIa inhibitor (50 mug/mL corn trypsin inhibitor [CTI]) or elastase/cathepsin G inhibitors (Methoxysuccinyl-Ala-Ala-Pro-Ala-Chloromethyl-Ketone/Z-Gly-Leu-Phe-CMK, 100 mu mol/L) indicated that neutrophils can capture short fibrin strands flowing in recalcified PFP lacking CTI and can also promote thrombin generation through pathways attenuated by inhibitors of factor XIIa, elastase, and cathepsin G. When neutrophils were allowed to interact with platelets on a fibrinogen surface before perfusion of recalcified CTI-treated PFP, the fibrin deposition was observed to be dramatic compared with that over surfaces coated with platelets alone or neutrophils alone and compared with that formed on platelets adherent to collagen. This neutrophil promotion of platelet-mediated fibrin formation was attenuated by inhibitors of elastase or cathepsin G but not anti-tissue factor antibody. Neutrophils can interact with platelets via released proteases to increase platelet procoagulant activity and fibrin formation in CTI-treated plasma under the low-flow conditions expected in venous thrombosis or inflammation.