Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor
Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor
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DOI：
10.1016/j.thromres.2017.06.001
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发表时间：
2017-08-01
影响因子：
7.5
通讯作者：
Iida, Hiroki
中科院分区：
文献类型：
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作者：
Onuma, Takashi;Tanabe, Kumiko;Iida, Hiroki
1-磷酸鞘氨醇(S1P)是一种细胞外因子，通过与S1P受体(S1PR)结合，作为一种有效的脂质介质发挥作用。然而，S1P在表达S1PR的人血小板中的确切作用尚未完全阐明。我们以前报道过热休克蛋白27(HSP27)是在胶原蛋白的刺激下从人血小板释放的，伴随着它的磷酸化。在本研究中，我们观察了S1P对胶原诱导的血小板活化的影响。S1P预处理可明显减弱胶原诱导的聚集作用。S1P和胶原共同刺激可抑制胶原诱导的血小板活化，但作用弱于S1P预处理。S1P显著降低胶原刺激的血小板衍生生长因子(PDGF)-AB的分泌和可溶性CD40配体(SCD40L)的释放。此外，S1P还抑制胶原诱导的HSP27的释放和HSP27的磷酸化。S1P显著抑制胶原诱导的p38丝裂原活化蛋白激酶的磷酸化。S1P增加与S1PPR1和/或S1PR4偶联的GTP结合的GAI和GTP结合的Gα13水平。选择性S1PR4激动剂CYM50260抑制胶原刺激的血小板聚集、PDGF-AB分泌和sCD40L释放，而选择性S1PR1激动剂SEW2871则无此作用。此外，CYM50260还减少了胶原蛋白对磷酸化的HSP27的释放以及HSP27的磷酸化。选择性S1PR4拮抗剂CYM50358不影响胶原诱导的HSP27磷酸化，但能逆转S1P诱导的胶原对HSP27磷酸化的抑制作用。这些结果有力地表明，S1P通过S1PR4抑制胶原诱导的人血小板活化，而不是S1PR1。(C)2017爱思唯尔有限公司。保留所有权利。
Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation. Co-stimulation with S1P and collagen suppressed collagen-induced platelet activation, but the effect was weaker than that of S1P-pretreatment. The collagen-stimulated secretion of platelet-derived growth factor (PDGF)-AB and the soluble CD40 ligand (sCD40L) release were significantly reduced by S1P. In addition, S1P suppressed the collagen-induced release of HSP27 as well as the phosphorylation of HSP27. S1P significantly suppressed the collagen-induced phosphorylation of p38 mitogen-activated protein kinase. S1P increased the levels of GTP-bound Gai and GTP-bound G alpha 13 coupled to S1PPR1 and/or S1PR4. CYM50260, a selective S1PR4 agonist, but not SEW2871, a selective S1PR1 agonist, suppressed the collagen-stimulated platelet aggregation, PDGF-AB secretion and sCD40L release. In addition, CYM50260 reduced the release of phosphorylated-HSP27 by collagen as well as the phosphorylation of HSP27. The selective S1PR4 antagonist CYM50358, which failed to affect collagen-induced HSP27 phosphorylation, reversed the S1P-induced attenuation of HSP27 phosphorylation by collagen. These results strongly suggest that S1P inhibits the collagen-induced human platelet activation through S1PR4 but not S1PR1. (C) 2017 Elsevier Ltd. All rights reserved.