Role of chemotactic factor inactivator in modulating alveolar macrophage-derived neutrophil chemotactic activity

The stimulated alveolar macrophage is a potent source of neutrophil chemotactic activity. The release of this chemotactic activity can be inhibited by pretreating alveolar macrophages with anti-C5 antibody. We hypothesized that C5a, a fragment cleaved from C5 when C5 is activated, might activate the alveolar macrophage to release neutrophil chemotactic activity and that chemotactic factor inactivator, a serum inhibitor of C5a, could decrease this release. Activated complement components including C5a were found to stimulate guinea pig macrophages to release chemotactic activity into their culture supernatants at levels that were significantly higher than the chemotactic activity of C5a alone (P less than 0.001). Chemotactic factor inactivator was found to cause a marked reduction in the chemotactic activity released by macrophages stimulated with phagocytic and nonphagocytic stimuli (P less than 0.001, all comparisons). These data indicate that C5a can stimulate alveolar macrophages to release chemotactic activity in vitro, and that chemotactic factor inactivator may play a role in modulating this process.