A severe deficiency of coagulation factor VIIa results in attenuation of the asthmatic response in mice.
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.
Shinagawa
Kazuhiko
K
University of Notre Dame, Notre Dame, IN 46556, USA.
Ploplis
Victoria A
VA
Castellino
Francis J
FJ
D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000201:enzymology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D015942:Factor VIIa / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009077:Mucins / Q000378:metabolism; D010047:Ovalbumin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D009077:Mucins; D012333:RNA, Messenger; D010047:Ovalbumin; D013925:Thromboplastin; D015942:Factor VIIa