School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
J Thromb Haemost. 2012 Jun;10(6):1081-90. doi: 10.1111/j.1538-7836.2012.04745.x.
Fibrinogen and plasminogen strongly reduce adhesion of leukocytes and platelets to fibrin clots, highlighting a possible role for these plasma proteins in surface-mediated control of thrombus growth and stability. In particular, adsorption of fibrinogen on fibrin clots renders their surfaces non-adhesive, while the conversion of surface-bound plasminogen to plasmin by transiently adherent blood cells results in degradation of a superficial fibrin layer, leading to cell detachment. Although the mechanisms whereby these proteins exert their antiadhesive effects are different, the outcome is the same: the formation of a mechanically unstable surface that does not allow firm cell attachment.
Since fibrin clots in circulation are exposed to both fibrinogen and plasminogen, their combined effect on adhesion of monocytic cells was examined.
Fibrin gels were coated with plasminogen and its activation by adherent U937 monocytic cells in the presence of increasing concentrations of fibrinogen was examined by either measuring (125) I-labeled fibrin degradation products or plasmin amidolytic activity.
Unexpectedly, the antiadhesive effects of two fibrin binding proteins were not additive; in fact, in the presence of fibrinogen, the effect of plasminogen was strongly reduced. An investigation of the underlying mechanism revealed that fibrinogen prevented activation of fibrin-bound plasminogen by cells. Confocal microscopy showed that fibrinogen accumulates in a thin superficial layer of a clot, where it exerts its blocking effect on activation of plasminogen.
The results point to a complex interplay between the fibrinogen- and plasminogen-dependent antiadhesive systems, which may contribute to the mechanisms that control the adhesiveness of a fibrin shell on the surface of hemostatic thrombi.
纤维蛋白原和纤溶酶原可显著降低白细胞和血小板与纤维蛋白凝块的黏附，这突出表明这些血浆蛋白在表面介导的血栓生长和稳定性控制中可能发挥作用。特别是，纤维蛋白原在纤维蛋白凝块上的吸附使它们的表面不具有黏附性，而瞬态黏附的血细胞将表面结合的纤溶酶原转化为纤溶酶，导致浅层纤维蛋白层的降解，从而导致细胞脱落。尽管这些蛋白质发挥其抗黏附作用的机制不同，但结果是相同的：形成不允许牢固细胞附着的机械不稳定表面。
由于循环中的纤维蛋白凝块同时暴露于纤维蛋白原和纤溶酶原，因此研究了它们对单核细胞黏附的联合作用。
通过测量（125）I 标记的纤维蛋白降解产物或纤溶酶的 amidolytic 活性，研究了在存在不同浓度纤维蛋白原的情况下，纤溶酶原在纤维蛋白凝胶上的吸附及其在存在时被黏附的 U937 单核细胞激活的情况。
出乎意料的是，两种纤维结合蛋白的抗黏附作用不是相加的；实际上，在纤维蛋白原存在的情况下，纤溶酶原的作用大大降低。对潜在机制的研究表明，纤维蛋白原阻止了细胞激活纤维结合的纤溶酶原。共聚焦显微镜显示，纤维蛋白原在凝块的浅层中积聚，在那里它对纤溶酶原的激活产生阻断作用。
结果表明，纤维蛋白原和纤溶酶原依赖性抗黏附系统之间存在复杂的相互作用，这可能有助于控制止血血栓表面纤维蛋白壳的黏附性的机制。
