title: Subepithelial Accumulation of Versican in a Cockroach Antigen-Induced Murine Model of Allergic Asthma.
abstract: The extracellular matrix (ECM) is an important contributor to the asthmatic phenotype. Recent studies investigating airway inflammation have demonstrated an association between hyaluronan (HA) accumulation and inflammatory cell infiltration of the airways. The ECM proteoglycan versican interacts with HA and is important in the recruitment and activation of leukocytes during inflammation. We investigated the role of versican in the pathogenesis of asthmatic airway inflammation. Using cockroach antigen (CRA)-sensitized murine models of allergic asthma, we demonstrate increased subepithelial versican in the airways of CRA-treated mice that parallels subepithelial increases in HA and leukocyte infiltration. During the acute phase, CRA-treated mice displayed increased gene expression of the four major versican isoforms, as well as increased expression of HA synthases. Furthermore, in a murine model that examines both acute and chronic CRA exposure, versican staining peaked 8 days following CRA challenge and preceded subepithelial leukocyte infiltration. We also assessed versican and HA expression in differentiated primary human airway epithelial cells from asthmatic and healthy children. Increases in the expression of versican isoforms and HA synthases in these epithelial cells were similar to those of the murine model. These data indicate an important role for versican in the establishment of airway inflammation in asthma.
authors.affiliation: Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington (SRR, JSD)|Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington (SRR, JSD)
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Reeves
authors.affiliation: Matrix Biology Program,  Benaroya Research Institute, Seattle, Washington (GK, TNW)
authors.forename: Gernot
authors.initials: G
authors.lastname: Kaber
authors.affiliation: Immunology Program,  Benaroya Research Institute, Seattle, Washington  (AS, SFZ),
authors.forename: Alyssa
authors.initials: A
authors.lastname: Sheih
authors.affiliation: Department of Pathobiology, the Respiratory Institute, and Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio (GC, MAA)
authors.forename: Georgiana
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Department of Pathobiology, the Respiratory Institute, and Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio (GC, MAA)
authors.forename: Mark A
authors.initials: MA
authors.lastname: Aronica
authors.affiliation: Department of Anatomy and Medical Imaging, School of Medical Sciences, University of Auckland, Auckland, New Zealand (MJM)
authors.forename: Mervyn J
authors.initials: MJ
authors.lastname: Merrilees
authors.affiliation: Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington (SRR, JSD)|Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington (SRR, JSD)
authors.forename: Jason S
authors.initials: JS
authors.lastname: Debley
authors.affiliation: Department of Comparative Medicine and Center for Lung Biology, University of Washington, Seattle, Washington (CWF).
authors.forename: Charles W
authors.initials: CW
authors.lastname: Frevert
authors.affiliation: Immunology Program,  Benaroya Research Institute, Seattle, Washington  (AS, SFZ),
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.affiliation: Matrix Biology Program,  Benaroya Research Institute, Seattle, Washington (GK, TNW)
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
mesh_terms: D000293:Adolescent; D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D003058:Cockroaches / Q000276:immunology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053675:Versicans / Q000378:metabolism*
chemical_list: D000941:Antigens; C508323:Vcan protein, mouse; D053675:Versicans; D006820:Hyaluronic Acid
keywords: airway inflammation; asthma; cockroach antigen; extracellular matrix; hyaluronan; macrophages; versican