Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/808016
- Expression of kinin receptors on eosinophils: comparison of asthmatic patients and healthy subjects
Bertram, Cornelia M.;
Misso, Neil L.;
Figueroa, Carlos D.;
Foster, Paul S.;
Thompson, Philip J.;
Bhoola, Kanti D.
- The University of Newcastle. Faculty of Health, School of Biomedical Sciences and Pharmacy
- 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.
- Journal of Leukocyte Biology Vol. 85, Issue 3, p. 544-552
- Publisher Link
- Federation of American Societies for Experimental Biology
- Resource Type
- journal article