PHAGOCYTOSIS OF MAST-CELL GRANULES RESULTS IN DECREASED MACROPHAGE SUPEROXIDE PRODUCTION

THE mechanism by which phagocytosed mast cell granules (MCGs) inhibit macrophage superoxide production has not been defined. In this study, mt peritoneal macrophages were co-incubated with either isolated intac t MCGs or MCG-sonicate, and their respiratory burst capacity and morph ology were studied. Co-incubation of macrophages with either intact MC Gs or MCG-sonicate resulted in a dose-dependent inhibition of superoxi de-mediated cytochrome c reduction This inhibitory effect was evident within 5 min of incubation and with MCG-sonicate was completely revers ed when macrophages were washed prior to activation with PMA. In the c ase of intact MCGs, the inhibitory effect was only partially reversed by washing after a prolonged co-incubation time. Electron microscopic analyses revealed that MCGs were rapidly phagocytosed by macrophages a nd were subsequently disintegrated within the phagolysosomes. Assay of MCGs for superoxide dismutase (SOD) revealed the presence of signific ant activity of this enzyme. A comparison of normal macrophages and th ose containing phagocytosed MCGs did not reveal a significant differen ce in total SOD activity. It is speculated that, although there was no significant increase in total SOD activity in macrophages containing phagocytosed MCGs, the phagocytosed MCGs might cause a transient incre ase in SOD activity within the phagolysosomes. This transient rise In SOD results in scavenging of the newly generated superoxide. Alternati vely, MCG inhibition of NADPH oxidase would explain the reported obser vations.