MECHANISMS OF ACTIVATION OF THE CLASSICAL PATHWAY OF COMPLEMENT BY HAGEMAN-FACTOR FRAGMENT
MECHANISMS OF ACTIVATION OF THE CLASSICAL PATHWAY OF COMPLEMENT BY HAGEMAN-FACTOR FRAGMENT
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DOI：
10.1172/jci110898
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发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
KAPLAN, AP
中科院分区：
文献类型：
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作者：
GHEBREHIWET, B;RANDAZZO, BP;KAPLAN, AP
进一步阐明了激活的Hageman因子(HFF)片段激活血清或缺乏血小板的血浆中补体的经典途径的机制。当不同浓度的HFF与血清或低血小板血浆孵育时，总补体溶血活性呈剂量依赖性降低。这种激活似乎是由于HFF与大分子C1的直接相互作用，因为纯化的C1与HFF孵育会导致亚单位的解离，并伴随着C1r抗原性的降低，这表明C1的激活。用活性位点定向抑制剂H-D-Pro-苯丙氨酸-精氨酸氯甲基酮预先处理HFF，或用从玉米中提取的活性HF的特异性抑制剂处理HFF，可阻止HFF依赖的激活。用高纯度的C1r与HFF孵育也可以导致C1r的激活，通过使用合成底物直接或间接地通过C1s的激活和C2的消耗来评估。然而，HFF与高纯度的C1s孵育可形成活化的C1s(C1hivin.s)，但其激活效率低于HFF对C1r的激活。大分子C_1中的C_1的活化显然是由C_1R转化为C_1R的结果；C_1S的活化主要由C_1H_1R进行，其次是F的直接作用。
The mechanism by which a fragment of activated Hageman factor (HFf) activates the classical pathway of complement in serum or platelet-poor plasma was further delineated. When serum or platelet-poor plasma was incubated with various concentrations of HFf, the total complement hemolytic activity was reduced in a dose-dependent manner. This activation appears to be due to the direct interaction of HFf with macromolecular C1, since incubation of purified C1 with HFf resulted in dissociation of the subunits with concomitant reduction of C1r antigenicity that is indicative of C1 activation. HFf-dependent activation was prevented by prior treatment of HFf with the active site-directed inhibitor, H-D-proline-phenylalanine-arginine chloromethyl ketone or with a specific inhibitor of activated HF derived from corn. Incubation of HFf with highly purified C1r also resulted in activation of C1r as assessed directly using a synthetic substrate or indirectly by activation of C1s and consumption of C2. However, incubation of HFf with highly purified C1s resulted in formation of activated C1s (C1.hivin.s) but this was less efficient than HFf activation of C1r. Activation of C1 in macromolecular C1 apparently is the result of HFf conversion of C1r to C.hivin.1r; activation of C1s then occurs primarily by C.hivin.1r and to a lesser degree by the direct action of HFf.