title: Essential role of EP3 subtype in prostaglandin E2-induced adhesion of mouse cultured and peritoneal mast cells to the Arg-Gly-Asp-enriched matrix.
abstract: Accumulating evidence has indicated that mast cells can modulate a wide variety of immune responses. Migration and adhesion play a critical role in regulation of tissue mast cell function, in particular, under inflammatory conditions. We previously demonstrated that prostaglandin (PG) E(2) stimulates adhesion of a mouse mastocytoma cell line, P-815, to the Arg-Gly-Asp (RGD)-enriched matrix through cooperation between two PGE(2) receptor subtypes: EP3 and EP4 (Hatae N, Kita A, Tanaka S, Sugimoto Y, Ichikawa A. J Biol Chem 278: 17977-17981, 2003). We here investigated PGE(2)-induced adhesion of IL-3-dependent bone marrow-derived cultured mast cells (BMMCs). In contrast to the elevated cAMP-dependent adhesion of P-815 cells, EP3-mediated Ca(2+) mobilization plays a pivotal role in PGE(2)-induced adhesion of BMMCs. Adhesion and Ca(2+) mobilization induced by PGE(2) were abolished in the Ptger3(-/-) BMMCs and were significantly suppressed by treatment with pertussis toxin, a phospholipase C inhibitor, U-73122, and a store-operated Ca(2+) channel inhibitor, SKF 36965, indicating the involvement of G(i)-mediated Ca(2+) influx. We then investigated PGE(2)-induced adhesion of peritoneal mast cells to the RGD-enriched matrix. EP3 subtype was found to be the dominant PGE receptor that expresses in mouse peritoneal mast cells. PGE(2) induced adhesion of the peritoneal mast cells of the Ptger3(+/+) mice, but not that of the Ptger3(-/-) mice. In rat peritoneal mast cells, PGE(2) or an EP3 agonist stimulated both Ca(2+) mobilization and adhesion to the RGD-enriched matrix. These results suggested that the EP3 subtype plays a pivotal role in PGE(2)-induced adhesion of murine mast cells to the RGD-enriched matrix through Ca(2+) mobilization.
authors.affiliation: Dept. of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's Univ., Koshien, Nishinomiya, Hyogo 663-8179, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sakanaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ichikawa
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D007377:Interleukin-3 / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009842:Oligopeptides / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D037342:Pertussis Toxin / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D004963:Estrenes; D007377:Interleukin-3; D009842:Oligopeptides; D010726:Phosphodiesterase Inhibitors; C545648:Ptger3 protein, mouse; C545649:Ptger3 protein, rat; D011760:Pyrrolidinones; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C047981:arginyl-glycyl-aspartic acid; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D015232:Dinoprostone; D002118:Calcium