Seya T, Nagasawa S, Atkinson J P
Clin Exp Immunol. 1985 Oct;62(1):208-16.
Recent studies have concluded that after complement activation the final physiologic degradation products of C3 are C3c and the fragment of relative molecular mass (Mr) 42,000 which contains the C3d and C3g domains and was therefore named C3d,g. Using fluorescent labelled C3b as a substrate, we have determined the putative C3d,g ('C3d,g') producing activity of both normal and hereditary angioneurotic oedema (HANE) plasmas. In normal plasmas, the rate of production of C3d,g was 1.0 +/- 0.2 X 10(-10) mol/ml/h and this activity was blocked by antibodies to I. In contrast, HANE, plasmas (deficient in C1INH) showed more than twice as much 'C3d,g' production as normal plasmas and both antibodies to I and kallikrein were required to inhibit this activity. Because of this result, a more sensitive gel system was employed to detect the Mr 42,000 peptide and two 'C3d,g' fragments of approximately equal intensity with Mr of 42,000 and 43,000 were defined. Incubation of purified kallikrein with labelled iC3b produced a C3d,g-like fragment, C3d-k, that aligned with the band of 43,000 Mr generated in HANE plasma. These results indicate that HANE plasma, in contrast to normal plasma, generates the bioactive C3d-k fragment. C1INH blocks the activities of kallikrein and C1s, and C3d-k generation in HANE plasma is probably secondary to the proteolytic activity of kallikrein.
近期研究得出结论，补体激活后，C3的最终生理降解产物是C3c以及相对分子质量（Mr）为42,000的片段，该片段含有C3d和C3g结构域，因此被命名为C3d,g。我们以荧光标记的C3b为底物，测定了正常血浆和遗传性血管性水肿（HANE）血浆产生假定的C3d,g（“C3d,g”）的活性。在正常血浆中，C3d,g的产生速率为1.0±0.2×10⁻¹⁰mol/ml/h，且该活性被针对I的抗体所阻断。相比之下，HANE血浆（缺乏C1INH）产生的“C3d,g”比正常血浆多出两倍以上，并且需要针对I的抗体和激肽释放酶才能抑制该活性。基于这一结果，我们采用了更灵敏的凝胶系统来检测相对分子质量为42,000的肽，并确定了两条强度大致相等、相对分子质量分别为42,000和43,000的“C3d,g”片段。用纯化的激肽释放酶与标记的iC3b孵育产生了一个类似C3d,g的片段C3d-k，它与HANE血浆中产生的相对分子质量为43,000的条带一致。这些结果表明，与正常血浆不同，HANE血浆产生了具有生物活性的C3d-k片段。C1INH可阻断激肽释放酶和C1s的活性，HANE血浆中C3d-k的产生可能继发于激肽释放酶的蛋白水解活性。
