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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/L880    most recent 00499.2005v1 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 (8) Citing Articles via Google Scholar Google Scholar Articles by Szema, A. M. Articles by Said, S. I. Search for Related Content PubMed PubMed Citation Articles by Szema, A. M. Articles by Said, S. I.

Mice lacking the VIP gene show airway hyperresponsiveness and airway inflammation, partially reversible by VIP

Departments of ¹Medicine, ²Pathology, and ³Preventive Medicine, State University of New York at Stony Brook; ⁴Northport Veterans Affairs Medical Center, Northport, New York; and ⁵Department of Psychiatry, University of California at Los Angeles, California

Submitted 25 November 2005 ; accepted in final form 12 June 2006

The mechanisms leading to asthma, and those guarding against it, are yet to be fully defined. The neuropeptide VIP is a cotransmitter, together with nitric oxide (NO), of airway relaxation, and a modulator of immune and inflammatory responses. NO-storing molecules in the lung were recently shown to modulate airway reactivity and were proposed to have a protective role against the disease. We report here that mice with targeted deletion of the VIP gene spontaneously exhibit airway hyperresponsiveness to the cholinergic agonist methacholine as well as peribronchiolar and perivascular cellular infiltrates and increased levels of inflammatory cytokines in bronchoalveolar lavage fluid. Immunologic sensitization and challenge with ovalbumin generally enhanced the airway hyperresponsiveness and airway inflammation in all mice. Intraperitoneal administration of VIP over a 2-wk period in knockout mice virtually eliminated the airway hyperresponsiveness and reduced the airway inflammation in previously sensitized and challenged mice. The findings suggest that 1) VIP may be an important component of endogenous anti-asthma mechanisms, 2) deficiency of the VIP gene may predispose to asthma pathogenesis, and 3) treatment with VIP or a suitable agonist may offer potentially effective replacement therapy for this disease.

vasoactive intestinal peptide; asthma phenotype; knockout mice

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