ADHESIVE RECEPTOR MAC-1 COORDINATES THE ACTIVATION OF FACTOR-X ON STIMULATED CELLS OF MONOCYTIC AND MYELOID DIFFERENTIATION - AN ALTERNATIVE INITIATION OF THE COAGULATION PROTEASE CASCADE
ADHESIVE RECEPTOR MAC-1 COORDINATES THE ACTIVATION OF FACTOR-X ON STIMULATED CELLS OF MONOCYTIC AND MYELOID DIFFERENTIATION - AN ALTERNATIVE INITIATION OF THE COAGULATION PROTEASE CASCADE
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DOI：
10.1073/pnas.85.20.7462
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发表时间：
1988-10-01
影响因子：
11.1
通讯作者：
EDGINGTON, TS
中科院分区：
文献类型：
--
作者：
ALTIERI, DC;MORRISSEY, JH;EDGINGTON, TS
单核细胞通过调节组织因子的表面表达以及组织因子和因子 VII/活化因子 VII 形成的蛋白水解酶复合物的局部组装来启动凝血。我们现在表明，在缺乏这些起始分子的情况下，单核细胞和单核细胞/骨髓分化的细胞系可以在暴露于 ADP 后选择性地启动凝血。这种促凝血反应的分子基础由两个不同的事件组成。首先，ADP 刺激细胞诱导凝血因子 X 与表面粘附受体 Mac-1 的高亲和力结合。然后，Mac-1 浓缩的 X 因子在局部被快速蛋白水解裂解为具有活化 X 因子大小和活性特征的活性蛋白酶，支持细胞相关的凝血酶形成和促凝血反应。我们得出结论，单核细胞/骨髓粘附受体 Mac-1 具有意想不到的、特异性诱导的特性，可以组织分子组装，最终导致快速纤维蛋白形成，该纤维蛋白独立于组织因子和因子 VII/活化因子 VII 进行调节。
Monocytes initiate coagulation through regulated surface expression of tissue factor and local assembly of a proteolytic enzymatic complex formed by tissue factor and factor VII/activated factor VII. We now show that, in the absence of these initiating molecules, monocytes and cell lines of monocytic/myeloid differentiation can alternatively initiate coagulation after exposure to ADP. The molecular basis for this procoagulant response consists of two distinct events. First, cell stimulation with ADP induces high-affinity binding of coagulation factor X to the surface-adhesive receptor Mac-1. Locally, Mac-1-concentrated factor X is then rapidly proteolytically cleaved to an active protease with size and activity characteristics of activated factor X, which supports the cell-associated formation of thrombin and the procoagulant response. We conclude that the monocytic/myeloid adhesive receptor Mac-1 has the unexpected, specifically inducible property to organize a molecular assembly culminating in rapid fibrin formation that is independently regulated from tissue factor and factor VII/activated factor VII.