Schmaier A H
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0724, USA.
Thromb Haemost. 1997 Jul;78(1):101-7.
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.
总之，本文提出了对接触系统的一种修正观点。该系统与止血的起始关系不大。与狼疮抗凝物一样，接触蛋白缺乏会导致活化部分凝血活酶时间（APTT）延长，但可能是血栓形成的危险因素。激肽原产生的缓激肽（BK）是血管生物学的强效调节剂，可诱导血管舒张、组织纤溶酶原激活物释放和前列环素释放。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-凝血酶在精氨酸41后切割克隆的凝血酶受体。激肽原的α-凝血酶抑制活性存在于完整的激肽原、BK以及BK的所有降解产物中。高分子量激肽原（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，前激肽释放酶与HK结合后，会被一种独立于血浆因子XII活化形式的内皮细胞酶系统激活为激肽释放酶。内皮细胞上的前激肽释放酶激活会导致动力学上有利的单链尿激酶和纤溶酶原激活。因此，接触系统激活的“生理性负电荷表面”实际上是这些蛋白质在细胞膜上的组装以及被膜相关酶激活。
