Expression of kinin receptors on eosinophils : comparison of asthmatic patients and healthy subjects

C. Bertram, Neil Misso, Mirjana Fogel-Petrovic, C.D. Figueroa, P.S. Foster, Philip Thompson, Kanti Bhoola

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    20 Citations (Scopus)

    Abstract

    Eosinophils contribute to asthmatic airway inflammation by releasing cysteinyl leukotrienes (cysLT) and other inflammatory mediators, and bradykinin (BK) induces bronchoconstriction in asthmatic patients. The aims of this study were to investigate kinin receptor expression on eosinophils of asthmatic and healthy subjects and to assess the effects of kinin stimulation on eosinophils, which were isolated from peripheral blood of asthmatic (n=27) and healthy subjects (n=14). Kinin B1 and B2 receptors (B1R and B2R, respectively) and mRNA expression were investigated by quantitative confocal microscopy, flow cytometry, and RT-PCR. Intracellular Ca2+ was assessed by live-cell fluorescence confocal microscopy. Production of cysLT and eosinophil migration in response to BK and Lys-des[Arg9]-BK were assessed. Eosinophils expressed kinin B1R and B2R mRNA and proteins. Quantitative immunofluorescence analysis indicated that expression of B1R and B2R proteins was significantly greater in eosinophils of asthmatic patients compared with those of nonasthmatic subjects. However, kinin B1R and B2R mRNA expression did not differ significantly between these groups. Expression of kinin B1R and mRNA was decreased in patients using high doses of inhaled corticosteroids and in eosinophils treated with a corticosteroid in vitro. Kinin B1 and B2 agonists up-regulated expression of their respective receptors but did not increase intracellular Ca2+ or the production of cysLT or enhance eosinophil migration significantly. Up-regulation of kinin receptor expression in eosinophils of asthmatic patients may be a consequence of inflammation, whereby enhanced release of kinin peptides has a positive-feedback effect on kinin receptor expression. Importantly, anti-inflammatory corticosteroids down-regulated the expression of the kinin B1R.
    Original languageEnglish
    Pages (from-to)544-552
    JournalJournal of Leukocyte Biology
    Volume85
    Issue number3
    DOIs
    Publication statusPublished - 2009

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