Expression of prostaglandin E(2) receptor subtypes on cells in sputum from patients with asthma and controls: effect of allergen inhalational challenge

Background Prostaglandin (PG) E 2 binds to 4 G-protein–coupled receptors designated EP 1 through EP 4 . Although PGE 2 plays an immunomodulatory role in asthma, there is little information on the expression of PGE 2 receptors in this disease. Objective We hypothesized that profiles of E-prostanoid (EP) receptor expression are altered on asthmatic bronchial inflammatory cells in vivo and further altered by allergen challenge in vivo and proinflammatory mediators in vitro . Methods The numbers and phenotypes of EP 1-4 immunoreactive induced sputum cells from atopic asthmatics (n=13; before and 24 hours after allergen inhalational challenge) and normal controls (n=9; 3 after saline challenge) and EP 1-4 expression on purified blood eosinophils from both groups (n=4 for each) before and after stimulation with LPS and/or IL-5 in vitro were measured by using single and double immunocytochemistry. Results Subsets of sputum cells of all phenotypes expressed all 4 EP receptors in both patients with asthma and controls. There were significantly greater numbers of macrophages expressing all 4 EP receptors and increased percentages of macrophages expressing EP 2 and EP 4 in patients with asthma compared with controls. Allergen bronchial challenge of patients with asthma was associated with a selective influx of eosinophils, but the percentages of these and other leukocytes expressing all 4 EP receptors were unchanged. Compared with sputum, only small percentages of peripheral blood eosinophils expressed each receptor, but this was increased by culture with exogenous IL-5 or LPS. Conclusion E-prostanoid receptor expression is increased on airway macrophages of patients with asthma at baseline and may be altered on eosinophils after allergen challenge in vivo in response to inflammatory stimuli.