Nitric oxide and host defense against Pneumocystis carinii infection in a mouse model.
To investigate whether successful host defense against Pneumocystis carinii is dependent on induction of inducible nitric oxide synthase (iNOS) in alveolar macrophages, immunocompetent mice, mice depleted of CD4 lymphocytes with anti-CD4 antibody, and mice with severe combined immunodeficiency (scid) were inoculated intratracheally with P. carinii. Three weeks later, immunocompetent mice had cleared the organisms completely, while CD4 cell-depleted and scid mice were severely infected (scores, 3.6 +/- 0.2 and 2.8 +/- 0.2, respectively). Inflammation scores were significantly higher in CD4 cell-depleted mice (3.4 +/- 0.2) than in scid mice (0.6 +/- 0.2). Minimal iNOS mRNA was detectable in lung tissue from immunocompetent mice; iNOS mRNA was comparable in scid mice and mice inoculated with PBS but was 6-fold higher in CD4 cell-depleted mice. Immunohistochemistry localized iNOS protein to alveolar macrophages in CD4 cell-depleted mice. Thus, iNOS is an unlikely participant in host defense against P. carinii, because enzyme expression does not correlate with either clearance or severity of infection.
Shellito
J E
JE
Section of Pulmonary and Critical Care Medicine, Louisiana State University Medical Center, New Orleans 70112, USA.
Kolls
J K
JK
Olariu
R
R
Beck
J M
JM
D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D004790:Enzyme Induction; D007121:Immunocompetence; D016867:Immunocompromised Host; D007124:Immunoenzyme Techniques; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008212:Lymphocyte Depletion; D016676:Macrophages, Alveolar / Q000201:enzymology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D011010:Pneumocystis / Q000254:growth & development*; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013047:Specific Pathogen-Free Organisms
D017931:DNA Primers; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase