title: Nitric oxide and host defense against Pneumocystis carinii infection in a mouse model.
abstract: 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.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Louisiana State University Medical Center, New Orleans 70112, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Shellito
authors.forename: J K
authors.initials: JK
authors.lastname: Kolls
authors.forename: R
authors.initials: R
authors.lastname: Olariu
authors.forename: J M
authors.initials: JM
authors.lastname: Beck
mesh_terms: 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
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase