Immune and Functional Role of Nitric Oxide in a Mouse Model of Respiratory Syncytial Virus Infection

• Published in: The Journal of infectious diseases Vol. 191; no. 3; pp. 387 - 395
• Main Authors: Stark, James M., Khan, Amir M., Chiappetta, Constance L., Xue, Hasen, Alcorn, Joseph L., Colasurdo, Giuseppe N.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.02.2005; University of Chicago Press; Oxford University Press
• Subjects: Animal models; Animals; Biological and medical sciences; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - physiopathology; Bronchial Hyperreactivity - virology; Disease Models, Animal; Epithelial cells; Female; Fundamental and applied biological sciences. Psychology; Human respiratory syncytial virus; Infectious diseases; Lung - immunology; Lung - physiopathology; Lungs; Lymphocytes; Medical sciences; Mice; Mice, Inbred BALB C; Microbiology; Neutrophils; Nitric Oxide - metabolism; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; Oxides; Pneumonia; Respiratory syncytial virus; Respiratory syncytial virus infections; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - physiopathology; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Virus, Human - pathogenicity; Respiratory syncytial viruses; RNA, Messenger - genetics; RNA, Messenger - metabolism; Viruses; Infection; Animal model; Microbiology; Nitric oxide; Viral disease
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/427241

Background. Respiratory syncytial virus (RSV) infection of respiratory epithelial cell cultures increases expression of inducible nitric oxide synthase (iNOS). The present study was designed to evaluate both the effect of RSV infection on expression of iNOS and the role of NO in the host responses to RSV infection in vivo. Methods. RSV infection was performed by nasal inoculation of BALB/c mice (6–8 weeks old). Total cell and differential counts were measured in bronchoalveolar lavage (BAL) fluid. Lung nitrates were measured in BAL fluid by use of the Greiss reaction, and cytokines were measured by enzyme-linked immunosorbent assay. Lung hyperresponsiveness to methacholine was measured by use of a Buxco unrestrained whole-body plethysmograph. Results. RSV infection increased levels of lung nitrites, levels of iNOS protein and activity, and levels of iNOS mRNA. RSV infection resulted in recruitment of neutrophils and lymphocytes into the lungs, enhanced levels of interferon (IFN)-γ, and increased airway hyperresponsiveness (AHR). Treatment with iNOS inhibitors (2-amino-5,6-dihydro-6-mehyl-4H-1,3-thiazine and N-nitro-L-arginine methyl ester) increased RSV titers in the lungs yet reduced lung inflammation and RSV-induced AHR. Inhibition of iNOS activity with either agent did not significantly alter levels of (IFN)-γ or interleukin-4 in the lungs. Conclusions. The results of the present study suggest that RSV-induced production of NO participates in complex host responses and may mediate important aspects of the clinical disease.