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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/L763    most recent 90638.2008v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shinagawa, K. Articles by Castellino, F. J. Search for Related Content PubMed PubMed Citation Articles by Shinagawa, K. Articles by Castellino, F. J.

A severe deficiency of coagulation factor VIIa results in attenuation of the asthmatic response in mice

The W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana

Submitted 24 December 2008 ; accepted in final form 10 March 2009

Eosinophil counts in the bronchoalveolar lavage fluid of wild-type (WT) mice increased after ovalbumin (OVA) challenge, a response that was diminished in comparably challenged low-expressing coagulation factor VII (FVII^tTA/tTA) mice. Levels of T helper type 2 (Th2) cytokines, IL-4, IL-5, and IL-13, and eosinophil-attracting chemokines, eotaxin and RANTES, were also lower in the OVA-challenged FVII^tTA/tTA mice. Eosinophils purified from low-FVII mice underwent apoptosis at a faster rate compared with WT eosinophils, and eosinophil migration in response to eotaxin was reduced in eosinophils obtained from FVII^tTA/tTA mice. Airway hyperresponsiveness and mucous layer thickness were reduced in OVA-treated FVII^tTA/tTA mice, and addition of exogenous coagulation factor X (FX) enhanced mucin production in human epithelial NCI-H292 cells. Correspondingly, incubation of FX with NCI-H292 cells resulted in activated (a) FX production, suggesting that the components required for FX activation were present on NCI-H292 cells. These results demonstrate that FVIIa functions in the asthmatic response to an allergen by stimulating lung eosinophilia, airway hyperresponsiveness, and mucin production, this latter effect through its ability to activate FX in conjunction with tissue factor.

coagulation factor X; eosinophilia; T helper type 2 cytokines; chemokines; airway