Cellular expressin of Prostaglandin E 2 receptor EP 1-4 in induced sputum from atopic asthmatics : Effect of allergen inhalational challenge

Abstract

Rationale The eicosanoid prostaglandin E 2 (PGE 2) exerts a variety of patho/physiological effects via 4 G-protein-coupled receptors, EP 1–4. PGE 2 plays an immunomodulatory role in asthma (for example, it inhibits bronchospasm caused by allergen inhalational challenge), but there is little information on the expression of PGE 2 receptors in this disease. Methods Using immunocytochemistry with receptor-specific antibodies, we measured the numbers and phenotypes of EP 1–4 immunoreactive cells in cytospins of induced sputum obtained from atopic asthmatics (n=13) before and 24 hrs after allergen inhalational challenge. Results Prior to challenge, 25.1 ± 2.9%, 35.3 ± 4.4%, 18.1 ± 2.5% and 40.9 ± 7.6% of all sputum cells expressed immunoreactivity for EP 1–4, respectively. For all 4 receptors, macrophages compared 50–80%, neutrophils 10–40% and eosinophils 5–10% of total immunoreactive cells, with only a small percentage accounted for by lymphocytes, epithelial and squamous cells. Conversely, 20–80% of neutrophils, 10–30% of eosinophils, 20–40% macrophages and 2–10% of lymphocytes showed immunoreactivity for all 4 receptors. Following allergen challenge, there was a significant increase in the absolute numbers of sputum eosinophils, but not other cells, expressing all 4 receptors (p<0.05 in each case), with no significant change in the percentages of the total eosinophils immunoreactive for each receptor. Conclusions Inflammatory leukocytes in induced sputum of atopic asthmatics express all 4 PGE 2 receptors, and allergen challenge is associated with an influx of eosinophils expressing all 4 receptors. Our further preliminary data suggest that there is a low level of expression on peripheral blood eosinophils. This provides one possible mechanism for the anti-inflammatory effects of PGE 2 in asthma.