title: Factor XI deficiency enhances the pulmonary allergic response to house dust mite in mice independent of factor XII.
abstract: Asthma is associated with activation of coagulation in the airways. The coagulation system can be initiated via the extrinsic tissue factor-dependent pathway or via the intrinsic pathway, in which the central player factor XI (FXI) can be either activated via active factor XII (FXIIa) or via thrombin. We aimed to determine the role of the intrinsic coagulation system and its possible route of activation in allergic lung inflammation induced by the clinically relevant human allergen house dust mite (HDM). Wild-type (WT), FXI knockout (KO), and FXII KO mice were subjected to repeated exposure to HDM via the airways, and inflammatory responses were compared. FXI KO mice showed increased influx of eosinophils into lung tissue, accompanied by elevated local levels of the main eosinophil chemoattractant eotaxin. Although gross lung pathology and airway mucus production did not differ between groups, FXI KO mice displayed an impaired endothelial/epithelial barrier function, as reflected by elevated levels of total protein and IgM in bronchoalveolar lavage fluid. FXI KO mice had a stronger systemic IgE response with an almost completely absent HDM-specific IgG1response. The phenotype of FXII KO mice was, except for a higher HDM-specific IgG1response, similar to that of WT mice. In conclusion, FXI attenuates part of the allergic response to repeated administration of HDM in the airways by a mechanism that is independent of activation via FXII.
authors.affiliation: Center for Experimental and Molecular Medicine, University of Amsterdam, Amsterdam, the Netherlands; i.stroo@amc.uva.nl.|Department of Immunopathology, Sanquin Research, Amsterdam, the Netherlands; and.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Stroo
authors.affiliation: Center for Experimental and Molecular Medicine, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Jack
authors.initials: J
authors.lastname: Yang
authors.affiliation: Center for Experimental and Molecular Medicine, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: J Daan
authors.initials: JD
authors.lastname: de Boer
authors.affiliation: Department of Pathology, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Joris J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.affiliation: Center for Experimental and Molecular Medicine, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: van 't Veer
authors.affiliation: W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Castellino
authors.affiliation: Department of Immunopathology, Sanquin Research, Amsterdam, the Netherlands; and.|Department of Hematology, University of Amsterdam, Amsterdam, the Netherlands; and.
authors.forename: Sacha
authors.initials: S
authors.lastname: Zeerleder
authors.affiliation: Center for Experimental and Molecular Medicine, University of Amsterdam, Amsterdam, the Netherlands.|Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001992:Bronchoalveolar Lavage Fluid; D004804:Eosinophils / Q000378:metabolism; D005173:Factor XI Deficiency / Q000097:blood / Q000150:complications / Q000469:parasitology* / Q000473:pathology*; D005174:Factor XII / Q000378:metabolism*; D005342:Fibrinolysis; D006967:Hypersensitivity / Q000097:blood / Q000150:complications / Q000469:parasitology* / Q000473:pathology*; D008168:Lung / Q000469:parasitology / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D039981:Pyroglyphidae / Q000502:physiology*
chemical_list: D005174:Factor XII
keywords: allergy; coagulation; factor XI; factor XII; house dust mite