de Smet B J, de Boer J P, Agterberg J, Rigter G, Bleeker W K, Hack C E
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Blood. 1993 Jan 1;81(1):56-61.
C1-inhibitor is the only known inhibitor of the classical pathway of complement and the major inhibitor of the contact pathway of coagulation. Like other serine proteinase inhibitors, C1-inhibitor can exist in three conformations, ie, the native, the proteinase-complexed, and the proteolytically inactivated form. Here we studied the plasma elimination kinetics of these three forms of human C1-inhibitor in rats. The clearance of the complexed form of C1-inhibitor appeared to be the most rapid and depended in part on the proteinase involved (observed plasma t1/2 was 20 minutes for C1s-C1-inhibitor, 32 minutes for kallikrein-C1-inhibitor, and 47 minutes for beta XIIa-C1-inhibitor), whereas that of native C1-inhibitor was the slowest (observed plasma t1/2 4.5 hours). Inactivated C1-inhibitor was cleared with an apparent plasma t1/2 of 1.6 hours. Thus, the short plasma t1/2 of complexed relative to native C1-inhibitor explains why in patients only low concentrations of C1-inhibitor complexes may be observed despite activation of the contact and/or complement systems.
C1抑制剂是补体经典途径唯一已知的抑制剂以及凝血接触途径的主要抑制剂。与其他丝氨酸蛋白酶抑制剂一样，C1抑制剂可以以三种构象存在，即天然构象、与蛋白酶复合的构象和蛋白水解失活形式。在此，我们研究了这三种形式的人C1抑制剂在大鼠体内的血浆清除动力学。C1抑制剂复合形式的清除似乎最快，部分取决于所涉及的蛋白酶（观察到的血浆半衰期，C1s-C1抑制剂为20分钟，激肽释放酶-C1抑制剂为32分钟，β XIIa-C1抑制剂为47分钟），而天然C1抑制剂的清除最慢（观察到的血浆半衰期为4.5小时）。失活的C1抑制剂以1.6小时的表观血浆半衰期被清除。因此，与天然C1抑制剂相比，复合形式的血浆半衰期较短，这就解释了为什么在患者中尽管接触和/或补体系统被激活，但可能仅观察到低浓度的C1抑制剂复合物。
