INVIVO EFFECTS OF C3A ON NEUTROPHILS AND ITS CONTRIBUTION TO INFLAMMATORY LUNG PROCESSES IN A GUINEA-PIG MODEL

  • 1 March 1988
    • journal article
    • research article
    • Vol. 71  (3) , 486-492
Abstract
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 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.