Superoxide responses of immune complex-stimulated rat alveolar macrophages. Intracellular calcium and priming

ATP is known to induce calcium transients in rat and human neutrophils and to "prime" these cells for enhanced oxygen radical responses after stimulation with chemotactic peptide, FMLP, or immune complexes. Calcium ionophores are also well known for their ability to prime phagocytic cells. In the current studies, nonelicited rat alveolar macrophages were analyzed for the ability of ATP as well as FMLP, C5a, platelet-activating factor and calcium ionophore (A23187) to modify levels of intracellular calcium and to enhance superoxide anion (O2-) production in response to immune complexes. Although none of these agents induced a O2- response under the conditions employed, all, except FMLP and C5a (human, recombinant) increased intracellular calcium, although the temporal features of the increases varied with the agent. In contrast to the inability of FMLP and C5a to cause intracellular calcium increases in macrophages, these same peptides caused dose-dependent intracellular calcium increases in rat neutrophils, whether the cells were derived from the blood or from the peritoneal cavity. On the basis of the effects of EGTA, the calcium increases in alveolar macrophages were caused by intracellular release of calcium in addition to some influx of extracellular calcium. Although ATP caused a dose-related increase in the level of intracellular calcium in alveolar macrophages, the cells were not "primed" for enhanced O2- responses to immune complexes. In contrast, platelet-activating factor and A23187, each of which induced increased intracellular levels of calcium, were able to prime macrophages for enhanced O2- responses. C5a and FMLP neither increased intracellular calcium levels nor primed macrophages for enhanced O2- responses to immune complexes. It is not clear if the inability of ATP to prime alveolar macrophages is caused entirely by insufficient increases in intracellular calcium or if ATP is unable to bring about additional changes that are relevant to the priming phenomenon.