Essential role of EP3 subtype in prostaglandin E2-induced adhesion of mouse cultured and peritoneal mast cells to the Arg-Gly-Asp-enriched matrix
Essential role of EP3 subtype in prostaglandin E2-induced adhesion of mouse cultured and peritoneal mast cells to the Arg-Gly-Asp-enriched matrix
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DOI：
10.1152/ajpcell.00218.2008
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发表时间：
2008-11-01
影响因子：
5.5
通讯作者：
Ichikawa, Atsushi
中科院分区：
文献类型：
--
作者：
Sakanaka, Mariko;Tanaka, Satoshi;Ichikawa, Atsushi
张文忠，张文忠，张文忠. EP 3亚型在前列腺素E-2诱导的小鼠培养和腹腔肥大细胞与富含Arg-Gly-Asp基质的粘附中的重要作用美国生理学杂志细胞生理学295：C1427-C1433，2008年。首次发表于2008年9月24日; doi：10.1152/ajpcell.00218.2008。越来越多的证据表明，肥大细胞可以调节多种免疫反应。迁移和粘附在调节组织肥大细胞功能中起关键作用，特别是在炎症条件下。我们先前证明，前列腺素（PG）E-2通过两种PGE（2）受体亚型：EP 3和EP 4之间的合作，刺激小鼠肥大细胞瘤细胞系P-815粘附到富含Arg-Gly-Asp（RGD）的基质上（HoglycN，Kita A，Tanaka S，Sugimoto Y，Ichikawa A. J Biol Chem 278：17977-17981，2003）。我们研究了PGE（2）诱导IL-3依赖的骨髓来源的培养肥大细胞（BMMCs）的粘附。与P-815细胞的cAMP依赖性粘附增加相反，EP 3介导的Ca 2+动员在PGE（2）诱导的BMMC粘附中起关键作用。在Ptger 3（-/-）BMMC中，PGE（2）诱导的粘附和Ca 2+动员被消除，并且被百日咳毒素、磷脂酶C抑制剂U-73122和钙库操纵的Ca 2+通道抑制剂SKF 36965显著抑制，表明G（i）介导的Ca 2+内流参与其中。然后我们研究了PGE（2）诱导的腹腔肥大细胞与富含RGD的基质的粘附。结果表明，小鼠腹腔肥大细胞中主要表达EP 3亚型的PGE受体。PGE（2）E（2）可诱导Ptger 3（+）/（+）小鼠腹腔肥大细胞粘附，但对Ptger 3（-）/（-）小鼠腹腔肥大细胞无粘附作用。在大鼠腹腔肥大细胞中，PGE（2）或EP 3激动剂刺激Ca 2+动员和粘附到富含RGD的基质。这些结果表明，EP 3亚型在PGE（2）诱导的小鼠肥大细胞粘附到富含RGD的基质中起关键作用，通过Ca 2+动员。
Sakanaka M, Tanaka S, Sugimoto Y, Ichikawa A. Essential role of EP3 subtype in prostaglandin E-2-induced adhesion of mouse cultured and peritoneal mast cells to the Arg-Gly-Asp-enriched matrix. Am J Physiol Cell Physiol 295: C1427-C1433, 2008. First published September 24, 2008; doi: 10.1152/ajpcell.00218.2008.-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) 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 Ca2+ mobilization plays a pivotal role in PGE(2)-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 G(i)-mediated Ca2+ 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)E(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 Ca2+ 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 Ca2+ mobilization.