Comparison of kinin B(1) and B(2) receptor expression in neutrophils of asthmatic and non-asthmatic subjects.
Kinins have been implicated in the pathophysiology of asthma and activation of kinin receptors stimulates neutrophil chemotaxis. However, the expression of kinin receptors on neutrophils of asthmatic subjects has not been assessed. The aim of this study was to compare the expression of kinin B(1) and B(2) receptor mRNA and proteins in neutrophils of asthmatic and non-asthmatic subjects, and to assess whether inhaled corticosteroid treatment may influence expression of the kinin receptors. Neutrophils were isolated from peripheral blood of asthmatic (n=27) and non-asthmatic subjects (n=14). The presence of kinin B(1) and B(2) receptor protein on neutrophils was confirmed by immunolabeling with specific antibodies followed by immunoperoxidase, immunofluorescence and FACS detection. Kinin B(1) and B(2) receptor mRNA expression was assessed by RT-PCR. Quantitative image analysis of fluorescence immunolabeled neutrophils showed no differences in kinin B(1) or B(2) receptor protein expression between asthmatic and non-asthmatic subjects. Similarly, quantitative real time RT-PCR analysis demonstrated no differences in expression of mRNA for the kinin B(1) or B(2) receptors between asthmatic and non-asthmatic subjects. However, B(1) receptor mRNA expression was significantly lower in asthmatic subjects using > or =2000 microg of inhaled corticosteroid per day (p<0.05) and B(1) receptor protein levels also tended to be lower in these subjects. Corticosteroids may have a beneficial anti-inflammatory effect in asthma by down-regulating B(1) receptor expression on neutrophils, thereby decreasing the migration of these inflammatory cells into the airways.
Bertram
Cornelia
C
Lung Institute of Western Australia and Centre for Asthma, Allergy & Respiratory Research, The University of Western Australia, Perth, Australia.
Misso
Neil L
NL
Fogel-Petrovic
Mirjana
M
Figueroa
Carlos
C
Thompson
Philip J
PJ
Bhoola
Kanti D
KD
D000280:Administration, Inhalation; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D001507:Beclomethasone / Q000627:therapeutic use; D002633:Chemotaxis / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007705:Kinins; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D014176:Protein Biosynthesis / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000276:immunology; D043783:Receptor, Bradykinin B1 / Q000235:genetics* / Q000276:immunology; D043782:Receptor, Bradykinin B2 / Q000235:genetics* / Q000276:immunology; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology
D018927:Anti-Asthmatic Agents; D007705:Kinins; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D001507:Beclomethasone