Structural changes of plasma high molecular weight kininogen after in vitro activation and in sepsis.
Structural changes of plasma high molecular weight kininogen after in vitro activation and in sepsis.
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发表时间：
1988-08
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通讯作者：
A. Schmaier;A. Farber;R. Schein;C. Sprung
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作者：
A. Schmaier;A. Farber;R. Schein;C. Sprung
高分子量激肽原（HMWK）是一种多功能蛋白质，是缓激肽的母体分子、凝血辅因子和半胱氨酸蛋白酶抑制剂。在免疫印迹中，非还原型血浆HMWK通常在140 kd和120 kd处为两条带;还原型血浆HMWK在120 kd处为一条带。在浓度依赖性和时间依赖性实验中，高岭土活化的正常血浆HMWK以有序序列裂解。当非还原时，高岭土活化血浆中免疫印迹上的HMWK大小从140 kd条带变化到120 kd中间体，从而产生稳定的100 kd蛋白。当还原时，高岭土活化血浆中免疫印迹上的HMWK从单一的120 kd条带通过56 kd中间体变化为稳定的46 kd蛋白质。当使用可溶性激活剂硫酸葡聚糖刺激系统时，发生血浆HMWK的类似切割序列。高岭土活化后血浆HMWK的裂解在因子XI缺乏的血浆中与正常血浆中类似地发生，但在前激肽释放酶缺乏的血浆中减少。前激肽释放酶缺乏血浆的延长高岭土活化导致HMWK裂解为低于120 kd的条带。在长期高岭土活化因子XII缺乏的血浆中，血浆HMWK没有低于120 kd的条带。在一些脓毒症患者中，即使患者有其他接触系统激活的证据，也可能未观察到可检测到的血浆HMWK裂解至低于120 kd的条带。总之，这些研究表明，免疫印迹上血浆HMWK的某些裂解模式表明接触系统的预先激活。然而，在单一血浆中不存在这些切割形式的血浆HMWK并不排除接触活化的发生。
High molecular weight kininogen (HMWK) is a multifunctional protein that is a parent molecule for bradykinin, a cofactor for coagulation, and an inhibitor of cysteine proteases. On immunoblot, nonreduced plasma HMWK is usually two bands at 140 kd and 120 kd; reduced plasma HMWK is a single band at 120 kd. In both concentration-dependent and time-dependent experiments kaolin-activated normal plasma HMWK becomes cleaved in an ordered sequence. When nonreduced, HMWK on immunoblot in kaolin-activated plasma changes in size from a 140 kd band through a 120 kd intermediate to result in a stable 100 kd protein. When reduced, HMWK on immunoblot in kaolin-activated plasma changes from a single 120 kd band through a 56 kd intermediate to result in a stable 46 kd protein. A similar sequence of cleavage of plasma HMWK occurs when the soluble activator dextran sulfate is used to stimulate the system. Cleavage of plasma HMWK after kaolin activation occurs similarly in factor XI-deficient plasma as in normal plasma but is decreased in prekallikrein-deficient plasma. Prolonged kaolin activation of prekallikrein-deficient plasma results in HMWK cleavage to bands below 120 kd. No band of plasma HMWK below 120 kd appears in prolonged kaolin-activated factor XII-deficient plasma. In some patients with sepsis, detectable cleavage of plasma HMWK to bands below 120 kd may not be seen, even though the patient has other evidence for contact system activation. In conclusion, these studies indicate that certain cleaved patterns of plasma HMWK on immunoblot indicate prior activation of the contact system. However, the absence of these cleaved forms of plasma HMWK in a single plasma does not exclude the occurrence of contact activation.