Enhanced Macrophage Anti-Microbial Activity Following Dimethylnitrosamine Exposure in Vivo is Related to Augmented Production of Reactive Oxygen Metabolites

Abstract

Previous results demonstrated that mice exposed in vivo to DMN were more resistant to both bacterial and tumor challenges. Furthermore, macrophages (MØ) isolated from these animals demonstrated increased functional properties. As reactive oxygen intermediates (ROI) represent a key mechanism of antimicrobial action, it was important to determine whether ROI levels in MØ were related to augmented anti-microbial action in animals exposed to DMN in vivo. Peritoneal exudate MØ elicited with either thioglycollate (TG), Con A or C. parvum (CP) were examined for the production of ROIs. TG-MØ, Con A-MØ and CP-MØ obtained from animals exposed to DMN showed increased superoxide anion (O₂) production in vitro following stimulation with either phorbol myristate acetate (PMA) or opsonized zymosan (Op-zym) when compared to vehicle MØ. ROI production by bone marrow-derived macrophages (BMDM) produced by either GM-CSF or CSF-1 was also determined. BMDM from DMN-exposed animals obtained using either growth factor, had increased ROI production at 3, 5, 7 and 9 d of culture compared to vehicle BMDM. There was no shift in the kinetics of ROI production during differentiation of these BMDM. Analysis of extracellular anti-listericidal activity of TG-and CA-elicited MØ demonstrated that only TG-MØ obtained from DMN-exposed animals had enhanced killing capacity. There were no differences in intracellular anti-microbial activity in TG-and CA-elicited MØ obtained from either vehicle or DMN-exposed animals. TG-elicited