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This Article Full Text Full Text (PDF) All Versions of this Article: 286/2/L388    most recent 00286.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Lan, R. S. Articles by Henry, P. J. Search for Related Content PubMed PubMed Citation Articles by Lan, R. S. Articles by Henry, P. J.

Altered expression and in vivo lung function of protease-activated receptors during influenza A virus infection in mice

¹Pharmacology Unit, School of Medicine and Pharmacology, Faculty of Medicine and Dentistry, ²Discipline of Microbiology, School of Biomedical and Chemical Sciences, Faculty of Life Sciences, and ³Western Australian Institute for Medical Research, University of Western Australia, Perth, Australia 6009

Submitted 21 August 2003 ; accepted in final form 24 October 2003

Protease-activated receptors (PARs) are widely distributed in human airways, and recent evidence indicates a role for PARs in the pathophysiology of inflammatory airway disease. To further investigate the role of PARs in airway disease, we determined the expression and function of PARs in a murine model of respiratory tract viral infection. PAR-1, PAR-2, PAR-3, and PAR-4 mRNA and protein were expressed in murine airways, and confocal microscopy revealed colocalization of PAR-2 and cyclooxygenase (COX)-2 immunostaining in basal tracheal epithelial cells. Elevated levels of PAR immunostaining, which was particularly striking for PAR-1 and PAR-2, were observed in the airways of influenza A/PR-8/34 virus-infected mice compared with sham-infected mice. Furthermore, increased PAR-1 and PAR-2 expression was associated with significant changes in in vivo lung function responses. PAR-1 agonist peptide potentiated methacholine-induced increases in airway resistance in anesthetized sham-infected mice (and in indomethacin-treated, virus-infected mice), but no such potentiation was observed in virus-infected mice. PAR-2 agonist peptide transiently inhibited methacholine-induced bronchoconstriction in sham-infected mice, and this effect was prolonged in virus-infected mice. These findings suggest that during viral infection, the upregulation of PARs in the airways is coupled to increased activation of COX and enhanced generation of bronchodilatory prostanoids.

cyclooxygenase; airway resistance; epithelium

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