Production of nitric oxide by rat alveolar macrophages stimulated by Cryptococcus neoformans or Aspergillus fumigatus

Cryptococcus neoformans and Aspergillus fumigatus are airborne fungi and th e alveolar macrophages (AM) constitute a first line of host defence against both pathogens. We investigated the ability of rat AM to produce nitric ox ide (NO) when challenged in vitro with C. neoformans, A. fumigatus conidia or inert silica particles alone and together with interferon gamma (IFN-gam ma). The role of NO in the killing of C. neoformans as well as the relation ship between phagocytosis of the yeast or A. fumigatus conidia and NO produ ction by AM were studied. Both fungi, but not the inert particles induced a small but significant increase in NO production by AM. A synergistically e nhanced NO production by AM was observed when each fungus, but not silica p articles, were incubated together with IFN-gamma. AM treated with IFN-gamma and challenged with C. neoformans showed higher killing activity than untr eated AM, a finding that correlated with increased NO production by AM. Bot h effects were reduced by an inhibitor of NO synthesis. Increased NO produc tion by IFN-gamma activated AM was found together with an increased accumul ated attachment of A. fumigatus conidia and serum opsonized, but not unopso nized C. neoformans. The IFN-gamma dependent increase in accumulated attach ment of the fungi might be responsible for the synergistic effect of the fu ngi and IFN-gamma on the NO production. Our data suggest that activated rat AM might efficiently use the antimicrobial nitric oxide system in the defe nce against these pathogens in the normal host.