C5a generation in vitro by cell bound classical pathway convertase (EAC1423) was studied to determine whether there was any contribution to its expression by C6-9, the later acting complement components. It was shown that the presence of terminal components during activation of C5 allowed expression of markedly greater levels of C5a antigen and biological activity although consumption of C5 substrate was similar whether or not the terminal components were present. Free C5a antigen detected by radioimmunoassay correlated with C5a biological activity assessed by polymorphonuclear myeloperoxidase release. These findings describe a new role for the human terminal complement components in expression of biologically active C5a. Aspergillus fumigatus produces a water-soluble material which inhibits opsonization of fungal cells by normal human serum. This complement inhibitor (C.I.) was shown to decrease binding of the activated form of C3, C3b, to fungal surfaces by blocking alternative pathway activation. It appears to interfere with C3b deposition or activation. Since A. flavus, which is also a pathogen for humans produced this C.I. but A. niger did not, we speculate that in vivo production of C.I. may represent a pathogenesis factor for Aspergillus species by inhibition of opsonic, and chemotactic factors. We plan to purify this complement inhibitor to analyze its structure and using purified complement components determine its site of action in blockade of C3b deposition.
