Kane M A, May J E, Frank M M
J Clin Invest. 1973 Feb;52(2):370-6. doi: 10.1172/JCI107193.
The contributions of the classical and alternate pathways of complement activation to the biological effects of endotoxin have been examined in the guinea pig, with particular reference to thrombocytopenia, leukopenia, and the development of the hypercoagulable state. Injection of endotoxin into normal guinea pigs led to a 95% fall in the level of circulating platelets within 15 min as well as a fall in circulating granulocytes. C4-deficient guinea pigs, known to have a complete block in the activity of the classical complement pathway, but with the alternate pathway intact, sustained no fall in platelets. The development of granulocytopenia proceeded normally. Endotoxin did activate the alternate complement pathway in C4D guinea pigs, as evidenced by the fall in C3-9 titers. With restoration of serum C4 levels, endotoxin-induced thrombocytopenia was observed in C4D animals. Thus, function of the classical complement pathway was an absolute requirement for the development of thrombocytopenia. Experiments performed in cobra venom factor (CVF)-treated normal guinea pigs, with normal levels of C1, C4, and C2, but with less than 1% of serum C3-9 demonstrated the importance of the late components in the development of thrombocytopenia but not leukopenia.C4-deficient guinea pigs had normal clotting times demonstrating that C4 was not required for normal clotting. In addition, development of the hypercoagulable state, evidenced by a marked shortening of the clotting time, was not observed on injection of endotoxin into C4D animals. Therefore, development of the hypercoagulable state paralleled the development of thrombocytopenia and required function of the classical complement pathway. Again, the importance of the late components of complement was emphasized by the failure of CVF-treated normal animals to develop hypercoagulability. These results demonstrate that endotoxin is capable of activating both the classical and alternate complement pathways in guinea pigs but that function of the classical pathway is an absolute requirement for the development of thrombocytopenia and the hypercoagulable state.
在豚鼠中研究了补体激活的经典途径和替代途径对内毒素生物学效应的影响，特别涉及血小板减少、白细胞减少和高凝状态的发展。向正常豚鼠注射内毒素导致15分钟内循环血小板水平下降95%，同时循环粒细胞也减少。已知C4缺陷豚鼠的经典补体途径活性完全受阻，但替代途径完整，其血小板没有下降。粒细胞减少的发展过程正常。内毒素确实激活了C4缺陷豚鼠的替代补体途径，C3 - 9滴度下降证明了这一点。随着血清C4水平的恢复，在C4缺陷动物中观察到内毒素诱导的血小板减少。因此，经典补体途径的功能是血小板减少发生的绝对必要条件。在经眼镜蛇毒因子（CVF）处理的正常豚鼠中进行的实验表明，其C1、C4和C2水平正常，但血清C3 - 9含量低于1%，这证明了补体后期成分在血小板减少而非白细胞减少发展中的重要性。C4缺陷豚鼠的凝血时间正常，表明正常凝血不需要C4。此外，向C4缺陷动物注射内毒素后未观察到高凝状态的发展，高凝状态的特征是凝血时间明显缩短。因此，高凝状态的发展与血小板减少的发展平行，并且需要经典补体途径的功能。同样，CVF处理的正常动物未能发展出高凝性，这再次强调了补体后期成分的重要性。这些结果表明，内毒素能够激活豚鼠的经典和替代补体途径，但经典途径的功能是血小板减少和高凝状态发展的绝对必要条件。
