Prostaglandin E 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.


OBJECTIVE
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 auto-analyzer.


RESULTS
Of the prostanoid receptor agonists tested, the prostaglandin E2 (PGE2) receptor (EP receptor) agonist PGE2 (10(-7) to 10(-11) M) produced concentration-related potentiation of IgE-mediated histamine release from the cultured mast cells. Sulprostone, an EP1/EP3 agonist, SC-46275, a selective EP3 agonist, and 11-deoxy-PGE1, a selective EP2/EP3/EP4 agonist also caused a significant increase in histamine release induced by anti-IgE. BW245C, fluprostone, cicaprost and U46619 for the prostaglandin D2, F2alpha, I2, and thromboxane A2 receptors respectively, and the EP2/EP4 receptor agonist butaprost had little effect on anti-IgE stimulated histamine release from mast cells.


CONCLUSIONS
The present results suggest that PGE2 potentiates the IgE-mediated histamine release from the cultured mast cell via EP3 and/or EP1 receptors.
Wang
X S
XS
Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, New Territories, Hong Kong, China.
Lau
H Y A
HY
D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D001773:Blood Cells / Q000166:cytology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype
C545635:PTGER1 protein, human; C545647:PTGER3 protein, human; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; C072122:SC-46275; D000527:Alprostadil; D015232:Dinoprostone