Adenovirus infection increases iNOS and peroxynitrite production in the lung

Zsuzsanna K. Zsengellér, Gary F. Ross, Bruce C. Trapnell, Csaba Szabó, Jeffrey A. Whitsett

    Research output: Contribution to journalArticle

    12 Scopus citations

    Abstract

    Host inflammatory and immune responses limit viral gene expression after administration of replication-deficient adenoviruses to the lung. The current study asks whether inducible nitric oxide synthase (iNOS) expression and peroxynitrite generation accompanied the inflammatory response following intratracheal administration of adenovirus. Pulmonary iNOS mRNA and protein were increased 2, 7, and 14 days following administration of 2 × 109 plaque-forming units of recombinant adenovirus (Av1Luc1) to BALB/c mice. Adenovirus infection was associated with a marked increase in nitrotyrosine staining. Intense nitrotyrosine staining was observed in alveolar macrophages, respiratory epithelial cells, conducting airways, and alveolar spaces 2 days postinfection. Two weeks after exposure to adenovirus, nitrotyrosine staining was detected within alveolar macrophages, suggesting adenovirus enhanced the nitration of proteins that were subsequently taken up by alveolar macrophages. Western blot analysis using anti-nitrotyrosine antibody did not demonstrate accumulation of nitrated surfactant protein A (SP-A), although a small fraction of aggregated SP-A comigrated with a nitrotyrosine-positive protein. iNOS expression, peroxynitrite, and nitrotyrosine generation accompany and may contribute to inflammatory responses to adenovirus in the lung.

    Original languageEnglish (US)
    Pages (from-to)L503-L511
    JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
    Volume280
    Issue number3 24-3
    DOIs
    StatePublished - Mar 2001

    Keywords

    • Inducible nitric oxide synthase
    • Lung inflammation
    • Surfactant

    ASJC Scopus subject areas

    • Physiology
    • Pulmonary and Respiratory Medicine
    • Physiology (medical)
    • Cell Biology

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