EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE BY STIMULATED MACROPHAGES CORRELATES WITH THEIR ANTIHISTOPLASMA ACTIVITY

The antihistoplasma activity of recombinant murine gamma interferon (r MuIFN-gamma)-treated macrophages of the RAW 264.7 cell line depends on the generation of nitric oxide (NO.) from L-arginine. Macrophages of the P388D(1) cell line treated with rMuIFN-gamma do not produce NO. or inhibit the intracellular growth of Histoplasma capsulatum. NO. is ge nerated by the inducible enzyme nitric oxide synthase (INOS) formed by stimulated macrophages. Northern (RNA) blot analysis of RAW 264.7 cel ls revealed the expression of INOS mRNA after exposure to rMuIFN-gamma . In contrast, rMuIFN-gamma-treated P388D, cells did not produce detec table levels of iNOS. These data suggest that the failure of P388D, ce lls to generate NO. and to restrict the intracellular growth of H. cap sulatum is due to a lack of expression of iNOS following treatment wit h rMuIFN-gamma.