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 journalArticlepeer-review

14 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
Externally publishedYes

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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