Contact Activation: A Revision
Contact Activation: A Revision
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DOI：
10.1055/s-0038-1657509
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发表时间：
1997-07
影响因子：
6.7
通讯作者：
A. Schmaier
中科院分区：
文献类型：
--
作者：
A. Schmaier
最后，提出了接触系统的修正观点。该系统与止血的启动关系不大。与狼疮抗凝剂一样，接触蛋白的缺乏会延长APTT，但可能是血栓形成的危险因素。来自激肽原的BK是诱导血管舒张、组织纤溶酶原激活物释放和前列环素释放的血管生物学的有效调节剂。激肽原本身是α-凝血酶诱导的血小板活化的选择性抑制剂，可防止α-凝血酶在丝氨酸后裂解克隆的凝血酶受体41。激肽原的α-凝血酶抑制活性存在于完整的激肽原、BK和BK的所有分解产物中。HK也是内皮细胞上接触蛋白组装的关键蛋白。它是前激肽释放酶的受体，当与HK结合时，通过内皮细胞酶系统激活为激肽释放酶，而不依赖于血浆因子XII的活化形式。内皮细胞上的前激肽释放酶活化导致动力学上有利的单链尿激酶和纤溶酶原活化。因此，用于接触系统活化的“生理性带负电荷的表面”实际上是这些蛋白质在细胞膜上的组装和膜相关酶的活化。
In conclusion, a revised view of the contact system has been presented. This system has little to do with the initiation of hemostasis. Like lupus anticoagulants, deficiencies of contact proteins give prolonged APTTs but may be risk factors for thrombosis. BK from kininogens is a potent modulator of vascular biology inducing vasodilation, tissue plasminogen activator release, and prostacyclin liberation. Kininogens, themselves, are selective inhibitors of alpha-thrombin-induced platelet activation preventing alpha-thrombin from cleaving the cloned thrombin receptor after arginine41. Kininogens' alpha-thrombin inhibitory activity exists in intact kininogens, BK, and all of BK's breakdown products. HK also is the pivotal protein for contact protein assembly on endothelium. It is the receptor for prekallikrein which when bound to HK becomes activated to kallikrein by an endothelial cell enzyme system independent of activated forms of plasma factor XII. Prekallikrein activation on endothelial cells results in kinetically favorable single chain urokinase and plasminogen activation. Thus the "physiologic, negatively charged surface" for contact system activation is really the assembly of these proteins on cell membranes and activation by membrane-associated enzymes.