In vivo and in vitro NO2 exposures enhance phagocytic and tumoricidal activities of rat alveolar macrophages.

Abstract

Rat alveolar macrophages (AM) were exposed in vivo or in vitro to nitrogen dioxide (NO2) and subsequently tested for phagocytic and tumoricidal activities. AM obtained by lavage from Fischer 344/N rats exposed for 4 h to 40 ppm NO2 were significantly more phagocytic to opsonized sheep red blood cells (SRBC), exhibited an increased cytotoxic response toward syngeneic mammary adenocarcinoma cells, and were more sensitive to activation by agents such as lipopolysaccharide, muramyl dipeptide, and macrophage-activating factor, as compared with the response of AM obtained from unexposed control rats. Repeated 4 h/d NO2 exposures over 7-d or 14-d periods usually resulted in AM activity similar to control levels, with some instances of increased phagocytic activity of the AM but not to the extent of that observed for a single 4 h exposure. There were no significant decreases in the cytotoxic or phagocytic activities of the AM during any of the exposure periods. For the in vitro exposures, AM were lavaged from normal rats and then exposed for various periods to 10, 20, or 40 ppm NO2. A dose-related and time-dependent enhanced cytotoxic response of AM was observed. Maximum AM-mediated cytotoxicity occurred after an in vitro exposure to 10 ppm NO2 for 2 h. The cytotoxic response was directed toward syngeneic mammary adenocarcinoma cells but not against syngeneic embryoblast cells, indicating that the AM retained the ability to distinguish between normal and abnormal cells. No inhibitory effects of NO2 on AM-mediated cytotoxicity were observed. These experiments suggest that the host AM-mediated immune defense of the lung may be modulated by host exposure to inhaled chemicals.