NITRIC-OXIDE AND HOST-DEFENSE AGAINST PNEUMOCYSTIS-CARINII INFECTION IN A MOUSE MODEL

To investigate whether successful host defense against Pneumocystis ca rinii is dependent on induction of inducible nitric oxide synthase (iN OS) in alveolar macrophages, immunocompetent mice, mice depleted of CD 4 lymphocytes with anti-CD4 antibody, and mice with severe combined im munodeficiency (scid) were inoculated intratracheally with P. carinii. Three weeks later, immunocompetent mice had cleared the organisms com pletely, while CD4 cell-depleted and scid mice were severely infected (scores, 3.6 +/- 0.2 and 2.8 +/- 0.2, respectively), Inflammation scor es were significantly higher in CD4 cell-depleted mice (3.4 +/- 0.2) t han in scid mice (0.6 +/- 0.2). Minimal iNOS mRNA was detectable in lu ng tissue from immunocompetent mice; iNOS mRNA was comparable in scid mice and mice inoculated with PBS but was 6-fold higher in CD4 cell-de pleted mice, Immunohistochemistry localized iNOS protein to alveolar m acrophages in CD4 cell-depleted mice. Thus, iNOS is an unlikely partic ipant in host defense against P. carinii, because enzyme expression do es not correlate with either clearance or severity of infection.