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RECEPTORS AND SIGNAL TRANSDUCTION

Essential role of EP3 subtype in prostaglandin E₂-induced adhesion of mouse cultured and peritoneal mast cells to the Arg-Gly-Asp-enriched matrix

¹Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, and ²Institute for Biosciences, Mukogawa Women's University, Koshien, Nishinomiya, Hyogo; and ³Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto, Japan

Submitted 22 April 2008 ; accepted in final form 18 September 2008

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) E₂ stimulates adhesion of a mouse mastocytoma cell line, P-815, to the Arg-Gly-Asp (RGD)-enriched matrix through cooperation between two PGE₂ 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 PGE₂-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 Ca²⁺ mobilization plays a pivotal role in PGE₂-induced adhesion of BMMCs. Adhesion and Ca²⁺ mobilization induced by PGE₂ 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 Ca²⁺ channel inhibitor, SKF 36965, indicating the involvement of G_i-mediated Ca²⁺ influx. We then investigated PGE₂-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. PGE₂ induced adhesion of the peritoneal mast cells of the Ptger3^+/+ mice, but not that of the Ptger3^–/– mice. In rat peritoneal mast cells, PGE₂ or an EP3 agonist stimulated both Ca²⁺ mobilization and adhesion to the RGD-enriched matrix. These results suggested that the EP3 subtype plays a pivotal role in PGE₂-induced adhesion of murine mast cells to the RGD-enriched matrix through Ca²⁺ mobilization.

G_i; Ca²⁺ mobilization; store-operated Ca²⁺ channel; bone marrow-derived cultured mast cells