Submitted on April 22, 2008
Revised on August 19, 2008
Accepted on September 18, 2008
Essential role of EP3 subtype in prostaglandin E2-induced adhesion of mouse cultured and peritoneal mast cells to the Arg-Gly-Asp-enriched matrix
Mariko Sakanaka1, Satoshi Tanaka1*, Yukihiko Sugimoto2, and Atsushi Ichikawa3
1 School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University
2 Graduate School of Pharmaceutical Science, Kyoto University
3 Mukogawa Women's University
* To whom correspondence should be addressed. E-mail: s_tanaka{at}mukogawa-u.ac.jp.
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 co-operation between two PGE2 receptor subtypes, EP3 and EP4. 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 was significantly suppressed by treatment with pertussis toxin, a phospholipase C inhibitor, U73122, and a store-operated Ca2+ channel inhibitor, SK&F 36965, indicating the involvement of Gi-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.
