CELLULAR-RESPONSES OF GUINEA-PIG MACROPHAGES TO C4A - INHIBITION OF C3A-INDUCED O2- GENERATION BY C4A

We have investigated the cellular responses of guinea-pig macrophages to human C4a. C4a induced a biphasic Ca2+ mobilization; a rapid tempor ary Ca2+ mobilization from intracellular Ca2+ pool followed by a weak Ca2+ influx of extracellular Ca2+. Although the C4a-treated macrophage s did not respond again to C4a, that is, desensitization to C4a, the C 4a-desensitized macrophages still responded to C3a to induce a Ca2+ mo bilization. Furthermore, C4a failed to inhibit [I-125]-C3a binding to macrophages, suggesting that C4a receptors are different from C3a rece ptors. In contrast to C3a, C4a-induced Ca2+ mobilization didn't link t o O2- generation but inhibited the C3a-induced O2- generation. These r esults suggest that C4a binds to a specific C4a receptor on guinea-pig macrophages to down-regulate the C3a receptor-mediated O2- generation in macrophages.