Modulation of macrophage superoxide-induced cytochrome c reduction by mast cells

The effect of mast cells and mast cell granules on macrophage O2- release as determined by cytochrome c reduction was studied. In vitro activation of mast cells before macrophage activation caused a decrease in O2- -mediated cytochrome c reduction. This decrease was proportional to mast cell activation and reached 80% to 100% when mast cell mediator release was 40% to 50%. Incubation of isolated mast cell granules with macrophages before activation also inhibited O2- -mediated cytochrome c reduction in a dose-dependent manner. Mast cell granule-mediated inhibition of cytochrome c reduction was not caused by histamine, serotonin, or any other dialyzable components but was found to be caused by the scavenging of O2- by mast cell granule-bound superoxide dismutase. Macrophage uptake of sulfur 35-labeled mast cell granules, electron microscopic localization of mast cell granules in the macrophage phagosomes, and the abrogation of mast cell granule effect when the cells were preincubated at 0 degree C indicate that the effect was associated with the adherence or phagocytosis (or both) of mast cell granules. These results suggest that mast cell granules interact with macrophages and that granule superoxide dismutase scavenges O2- generated by the phagocytes.