Hoffmann T, Böttger E C, Baum H P, Messner M, Hadding U, Bitter-Suermann D
Institute of Medical Microbiology, University of Mainz, FRG.
Clin Exp Immunol. 1988 Mar;71(3):486-92.
C3a, when injected intravenously in guinea-pigs, caused a rapid drop of circulating neutrophils and platelets. The neutropenia was reversible and followed by a neutrophilia, which reached about 200% of baseline values. Upon challenge with octa- and hexapeptide, mimicking the C-terminal sequence of C3a, neutrophils and platelets reacted in the same manner. The hexapeptide-desArg (pentapeptide without the C-terminal arginine of hexapeptide) induced no neutropenia but a significant neutrophilia. Likewise, when injected in animals with a genetic deficiency or dysfunction of the C3a-receptor, the hexapeptide caused no drop of the neutrophils, but a neutrophilia, indicating that both neutrophil reactions are mediated by different mechanisms. With the octapeptide in vivo dose-response studies were performed. Despite maximal doses of octapeptide about 40% of the neutrophils remained in circulation, indicating that some but not all PMNs are susceptible to C3a. By pretreating the animals with an inhibitor of the serum carboxypeptidase N (SCPN-Inh) the C3a-induced neutropenia could be significantly augmented. But intravenous application of the inhibitor itself caused a 20-40% reduction of neutrophils during the first hour after injection, followed by a neutrophilia. In histological studies the timecourse of neutrophil sequestration in the lung was established, showing that the initial high neutrophil content of the lung lasted for at least 1 h and declined thereafter. Structural derangements could not be detected. These observations stress the importance of C3a besides C5a as an important mediator of inflammatory processes in species, where the C3a-receptor is present on inflammatory cells such as granulocytes.
将C3a静脉注射到豚鼠体内时，会导致循环中的中性粒细胞和血小板迅速减少。中性粒细胞减少是可逆的，随后会出现中性粒细胞增多，其数量达到基线值的约200%。用模拟C3a C末端序列的八肽和六肽进行攻击时，中性粒细胞和血小板的反应方式相同。六肽去精氨酸（不含六肽C末端精氨酸的五肽）不会引起中性粒细胞减少，但会导致显著的中性粒细胞增多。同样，当注射到C3a受体存在基因缺陷或功能障碍的动物体内时，六肽不会导致中性粒细胞减少，而是引起中性粒细胞增多，这表明两种中性粒细胞反应是由不同机制介导的。对八肽进行了体内剂量反应研究。尽管使用了最大剂量的八肽，但仍有约40%的中性粒细胞留在循环中，这表明部分但并非所有的多形核中性粒细胞对C3a敏感。通过用血清羧肽酶N抑制剂（SCPN - Inh）预处理动物，C3a诱导的中性粒细胞减少可显著增强。但静脉注射该抑制剂本身在注射后第一小时会导致中性粒细胞减少20 - 40%，随后会出现中性粒细胞增多。在组织学研究中确定了肺中中性粒细胞滞留的时间进程，结果显示肺中最初较高的中性粒细胞含量持续至少1小时，此后下降。未检测到结构紊乱。这些观察结果强调了在粒细胞等炎症细胞上存在C3a受体的物种中，C3a除了作为C5a之外，作为炎症过程的重要介质的重要性。
