title: Identification of Epithelial Phospholipase A2Receptor 1 as a Potential Target in Asthma.
abstract: Secreted phospholipase A2s (sPLA2s) regulate eicosanoid formation and have been implicated in asthma. Although sPLA2s function as enzymes, some of the sPLA2s bind with high affinity to a C-type lectin receptor, called PLA2R1, which has functions in both cellular signaling and clearance of sPLA2s. We sought to examine the expression of PLA2R1 in the airway epithelium of human subjects with asthma and the function of the murine Pla2r1 gene in a model of asthma. Expression of PLA2R1 in epithelial brushings was assessed in two distinct cohorts of children with asthma by microarray and quantitative PCR, and immunostaining for PLA2R1 was conducted on endobronchial tissue and epithelial brushings from adults with asthma. C57BL/129 mice deficient in Pla2r1 (Pla2r1-/-) were characterized in an ovalbumin (OVA) model of allergic asthma. PLA2R1 was differentially overexpressed in epithelial brushings of children with atopic asthma in both cohorts. Immunostaining for PLA2R1 in endobronchial tissue localized to submucosal glandular epithelium and columnar epithelial cells. After OVA sensitization and challenge, Pla2r1-/-mice had increased airway hyperresponsiveness, as well as an increase in cellular trafficking of eosinophils to the peribronchial space and bronchoalveolar lavage fluid, and an increase in airway permeability. In addition, Pla2r1-/-mice had more dendritic cells in the lung, higher levels of OVA-specific IgG, and increased production of both type-1 and type-2 cytokines by lung leukocytes. PLA2R1 is increased in the airway epithelium in asthma, and serves as a regulator of airway hyperresponsiveness, airway permeability, antigen sensitization, and airway inflammation.
authors.affiliation: From the 1 Division of Pulmonary and Critical Care and.
authors.forename: James D
authors.initials: JD
authors.lastname: Nolin
authors.affiliation: From the 1 Division of Pulmonary and Critical Care and.
authors.forename: H Luke
authors.initials: HL
authors.lastname: Ogden
authors.affiliation: From the 1 Division of Pulmonary and Critical Care and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lai
authors.affiliation: From the 1 Division of Pulmonary and Critical Care and.
authors.forename: William A
authors.initials: WA
authors.lastname: Altemeier
authors.affiliation: From the 1 Division of Pulmonary and Critical Care and.|2 Department of Comparative Medicine.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Frevert
authors.affiliation: 3 Department of Chemistry, and.
authors.forename: James G
authors.initials: JG
authors.lastname: Bollinger
authors.affiliation: 3 Department of Chemistry, and.
authors.forename: Gajendra S
authors.initials: GS
authors.lastname: Naika
authors.affiliation: 4 The Telethon Kids Institute, Centre for Health Research, University of Western Australia, Nedlands, Western Australia, Australia.|5 Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia.|6 School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia.|7 Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia; and.
authors.forename: Anthony
authors.initials: A
authors.lastname: Kicic
authors.affiliation: 4 The Telethon Kids Institute, Centre for Health Research, University of Western Australia, Nedlands, Western Australia, Australia.|5 Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia.|6 School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia.|7 Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia; and.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Stick
authors.affiliation: 8 Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Lambeau
authors.affiliation: 9 Division of Allergy and Infectious Diseases, Department of Medicine, and.
authors.forename: William R
authors.initials: WR
authors.lastname: Henderson
authors.affiliation: 3 Department of Chemistry, and.|10 Department of Biochemistry, University of Washington, Seattle, Washington.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.affiliation: From the 1 Division of Pulmonary and Critical Care and.
authors.forename: Teal S
authors.initials: TS
authors.lastname: Hallstrand
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid; D002648:Child; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D016210:Methacholine Chloride; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D009077:Mucins / Q000378:metabolism; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology; D054507:Receptors, Phospholipase A2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015656:Respiratory Mechanics
chemical_list: D000485:Allergens; D000941:Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D009077:Mucins; C516360:PLA2R1 protein, human; C516357:Pla2r1 protein, mouse; D054507:Receptors, Phospholipase A2; D016210:Methacholine Chloride
keywords: C-type lectin; allergy; asthma; phospholipase A2; phospholipase A2 receptor 1