Identification of epithelial phospholipase A2 receptor 1 as a potential target in asthma

J.D. Nolin, H.L. Ogden, Y. Lai, W.A. Altemeier, C.W. Frevert, J.G. Bollinger, G.S. Naika, Anthony Kicic, Stephen Stick, G. Lambeau, W.R. Henderson, M.H. Gelb, T.S. Hallstrand

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

© Copyright 2016 by the American Thoracic Society.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 OVAspecific 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.
Original languageEnglish
Pages (from-to)825-836
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume55
Issue number6
DOIs
Publication statusPublished - 2016

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