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This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/L890    most recent 00428.2004v1 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 (4) Citing Articles via Google Scholar Google Scholar Articles by Geary, C. Articles by Rice, W. Search for Related Content PubMed PubMed Citation Articles by Geary, C. Articles by Rice, W.

Increased susceptibility of purinergic receptor-deficient mice to lung infection with Pseudomonas aeruginosa

¹Division of Neonatology, University of Texas Medical Branch, Galveston, Texas; ²Division of Pulmonary Biology, Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio; and ³Cystic Fibrosis/Pulmonary and Research Treatment Center and ⁴Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Submitted 15 November 2004 ; accepted in final form 1 July 2005

Purinergic receptors are expressed throughout the respiratory system in diverse cell types. The efficiency of mucus clearance in the airways, the cascade leading to tissue injury, and inflammation are modulated by autocrine/paracrine release of nucleotides and signaling by purinergic receptors. We assessed the role of purinergic receptors in innate host defense of the lung in vivo by infecting mice deficient in P2Y₁, P2Y₂, or both receptors with intratracheal instillation of Pseudomonas aeruginosa. After P. aeruginosa challenge, all double knockout (P2Y₁/P2Y₂–/–) mice succumbed within 30 h of challenge, whereas 85% of the wild-type mice survived. Thirty-three percent of wild-type mice survived beyond 96 h. Single knockout mice, P2Y₁–/–, or P2Y₂–/–, exhibited intermediate survivals. Twenty-four hours following intratracheal instillation of a sublethal dose of P. aeruginosa, the level of total protein in bronchoalveolar lavage fluid was 1.8-fold higher in double knockout than in wild-type mice (P < 0.04). Total cell count in bronchoalveolar lavage fluids at 4 h and levels of IL-6 and macrophage inflammatory protein-2 in lung homogenates at 24 h postchallenge were significantly reduced in P2Y₁/P2Y₂–/– mice relative to wild-type mice. These findings suggest that purinergic receptors exert a protective role against infection of the lungs by P. aeruginosa by decreasing protein leak and enhancing proinflammatory cytokine response.

bacterial clearance; lungs; cystic fibrosis

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