TY - JOUR
T1 - Essential role of EP3 subtype in prostaglandin E2-induced adhesion of mouse cultured and peritoneal mast cells to the Arg-Gly-Asp-enriched matrix
AU - Sakanaka, Mariko
AU - Tanaka, Satoshi
AU - Sugimoto, Yukihiko
AU - Ichikawa, Atsushi
PY - 2008/11
Y1 - 2008/11
N2 - 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 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 Ca2+ channel inhibitor, SKF 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, PGE 2 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.
AB - 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 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 Ca2+ channel inhibitor, SKF 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, PGE 2 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.
KW - Bone marrow-derived cultured mast cells
KW - Ca mobilization
KW - G
KW - Store-operated Ca channel
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U2 - 10.1152/ajpcell.00218.2008
DO - 10.1152/ajpcell.00218.2008
M3 - Article
C2 - 18815228
AN - SCOPUS:57349108122
VL - 295
SP - C1427-C1433
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6143
IS - 5
ER -