Characterization of Macrophage Subsets Regulating Murine Natural Killer Cell Activity

Publisher Website
Google Scholar
Abstract
We examined the relationship of l-A expression by normal murine macrophages to their immunoregulatory role on natural killer cell activity. Macrophages were isolated on the basis of plastic adherence; characterized on the basis of conventional markers such as phagocytic ability, cytoplasmic non-specific esterase activity, surface MAC-1 and F4/80 antigen expression; and then used for functional studies relative to their expression of surface l-A. Two functional macrophage subsets were identified: NK-stimulatory and NK-suppressive subsets. The former function was associated with splenic macrophages, which were predominantly l-A+ as identified with a radioautographic immunolabeling technique; the latter function with peritoneal macrophages which were predominantly l-A-. Loss of macrophage l-A expression in vitro was delayed in the presence of indomethacin and enhanced in the presence of PGE2, indicating that PGE2 down-regulates l-A expression on macrophages. The NK stimulatory function of l-A+ macrophages was attributable to a soluble mediator, identified as IFN-γ, since the stimulatory ability was abrogated with an anti-IFN-γ antibody. l-A expression appears to be important for the stimulatory function, since some interference with this function was noted in the presence of anti-I-A antibody. The NK-suppressor function of I-A- macrophages was attributable to the soluble mediator PGE2, since this function was abrogated with indomethacin or anti-PGE2 antibody. These results are relevant to the understanding of normal in vivo immunoregulation by macrophages.