Prostaglandin E2 potentiates the immunologically stimulated histamine release from human peripheral blood-derived mast cells through EP1/EP3 receptors

Background: Mast cells cultured from human peripheral blood have been widely used to study human mast cell function. Prostanoids are the important regulators of mast cell activity, however, there were no reports about the class of prostanoid receptors expressed on such cultured cells. Aims: The present study was to characterize pharmacologically the prostanoid receptors by investigating the effects of prostanoid receptor agonists on the immunoglobulin E (IgE)-mediated histamine release from the cultured mast cells. Methods: Mast cells cultured from human progenitor cells in peripheral blood were sensitized with human myeloma IgE, and then challenged with anti-human IgE following pretreatment with diverse prostanoid receptor agonists. The histamine content in supernatants and cell pellets were measured by histamine autoanalyzer. Results: Of the prostanoid receptor agonists tested, the prostaglandin E 2 (PGE 2 ) receptor (EP receptor) agonist PGE 2 (10 -7 to 10 -11 M) produced concentration-related potentiation of IgE-mediated histamine release from the cultured mast cells. Sulprostone, an EP 1 /EP 3 agonist, SC-46275, a selective EP 3 agonist, and 11-deoxy-PGE 1 , a selective EP 2 /EP 3 /EP 4 agonist also caused a significant increase in histamine release induced by anti-IgE. BW245C, fluprostone, cicaprost and U46619 for the prostaglandin D 2 , F 2α , I 2 , and thromboxane A 2 receptors respectively, and the EP 2 /EP 4 receptor agonist butaprost had little effect on anti-IgE stimulated histamine release from mast cells. Conclusions: The present results suggest that PGE 2 potentiates the IgE-mediated histamine release from the cultured mast cell via EP 3 and/or EP 1 receptors.