RGD Reference Report - Defective Nitric Oxide Production by Alveolar Macrophages during Pneumocystis Pneumonia. - Rat Genome Database

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Defective Nitric Oxide Production by Alveolar Macrophages during Pneumocystis Pneumonia.

Authors: Lasbury, ME  Liao, CP  Hage, CA  Durant, PJ  Tschang, D  Wang, SH  Zhang, C  Lee, CH 
Citation: Lasbury ME, etal., Am J Respir Cell Mol Biol. 2010 Jun 17.
RGD ID: 4891486
Pubmed: (View Article at PubMed) PMID:20558778
DOI: Full-text: DOI:10.1165/rcmb.2009-0367OC

The toxicity of nitric oxide (NO) on Pneumocystis (Pc) organisms, the role of NO in the defense against Pc infection, and NO production by alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP) were investigated. Results indicated that NO was toxic to Pc organisms and inhibited their proliferation in culture. When NO production was inhibited by intraperitoneal injection of rats with the nitric oxide synthase inhibitor L-N5-(1-iminoethyl) ornithine (L-NIO), progression of Pc infection in immunocompetent rats was enhanced. NO levels in bronchoalveolar lavage (BAL) fluids from immunosuppressed, Pc-infected rats and mice were greatly reduced as compared to those from uninfected animals, and AMs from these animals were defective in NO production. However, inducible nitric oxide synthase (iNOS) mRNA and protein levels were high in AMs from Pc-infected rats and mice. Immunoblot analysis showed that iNOS in AMs from Pc-infected rats existed primarily as a monomer, but homo-dimerization of iNOS monomers was required for NO production. When iNOS dimerization cofactors, including calmodulin, were added to macrophage lysates, iNOS dimerization increased, whereas incubation of the same lysates with all cofactors except calmodulin did not rescue iNOS dimer formation. These data suggest that NO is important in the defense against Pc infection, but production of NO in AMs during PCP is defective due to reduced dimerization of iNOS.

Annotation

Disease Annotations    
pneumocystosis  (IEP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Nos2  (nitric oxide synthase 2)

Genes (Mus musculus)
Nos2  (nitric oxide synthase 2, inducible)

Genes (Homo sapiens)
NOS2  (nitric oxide synthase 2)


Additional Information