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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/C1427    most recent 00218.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sakanaka, M. Articles by Ichikawa, A. Search for Related Content PubMed PubMed Citation Articles by Sakanaka, M. Articles by Ichikawa, A.

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