Activation of the plasma kallikrein/kinin system on endothelial cell membranes
Activation of the plasma kallikrein/kinin system on endothelial cell membranes
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DOI：
10.1016/s0162-3109(99)00069-7
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发表时间：
1999-09-01
期刊：
影响因子：
--
通讯作者：
Schmaier, AH
中科院分区：
文献类型：
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作者：
Rojkjær, R;Schmaier, AH
三十多年来，人们已经知道，血浆激肽释放酶/激肽系统在暴露于人工带负电荷的表面时被激活。然而，在体内存在能够激活血浆激肽释放酶/激肽系统的包围性带负电荷的表面从未被令人信服地证明。在这份报告中，我们描述了目前的知识如何血浆激肽释放酶/激肽系统的蛋白质组装成为激活细胞膜上。在内皮细胞上，血浆激肽释放酶/激肽系统的激活不是由因子XII自激活启动的，如在人工表面上所见。在内皮细胞上，前激肽释放酶被抗疼痛敏感蛋白酶激活。前激肽释放酶的激活依赖于高分子量激肽原的存在和最佳游离Zn 2+浓度，在内皮细胞表面产生的激肽释放酶能够激活因子XII。此外，在内皮细胞膜上形成的激肽释放酶能够切割其受体和天然底物，高分子量激肽原，从内皮细胞表面释放缓激肽和HK.PK复合物。内皮细胞相关的激肽释放酶也能够动力学上有利的尿激酶原和随后的纤溶酶原激活。(C)1999 Elsevier Science B. V.保留所有权利。
For more than three decades, it has been known that the plasma kallikrein/kinin system becomes activated when exposed to artificial, negatively charged surfaces. The existence of an encompassing in vivo, negatively charged surface capable of activation of the plasma kallikrein/kinin system has, however, never been convincingly demonstrated. in this report, we describe current knowledge on how the proteins of the plasma kallikrein/kinin system assemble to become activated on cell membranes. On endothelial cells, the activation of the plasma kallikrein/kinin system is not initiated by factor XII autoactivation as seen on artificial surfaces. On endothelial cells, prekallikrein is activated by an antipain sensitive protease. Prekallikrein activation is dependent on the presence of high molecular weight kininogen and an optimal free Zn2+ concentration, Kallikrein generated on the surface of endothelial cell is capable of activating factor XII. Further, kallikrein formed on endothelial cell membranes is capable of cleaving its receptor and native substrate, high molecular weight kininogen, liberating bradykinin and the HK.PK complex from the endothelial cell surface. Endothelial cell-associated kallikrein also is capable of kinetically favorable pro-urokinase and, subsequent, plasminogen activation. (C) 1999 Elsevier Science B.V. All rights reserved.