Division of Pharmacology and Toxicology, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany.
Department of General Pharmacology, University Medicine Greifswald, 17489 Greifswald, Germany.
Int J Mol Sci. 2022 Sep 7;23(18):10278. doi: 10.3390/ijms231810278.
Sphingosine-1-phosphate (S1P) is a versatile signaling lipid involved in the regulation of numerous cellular processes. S1P regulates cellular proliferation, migration, and apoptosis as well as the function of immune cells. S1P is generated from sphingosine (Sph), which derives from the ceramide metabolism. In particular, high concentrations of S1P are present in the blood. This originates mainly from erythrocytes, endothelial cells (ECs), and platelets. While erythrocytes function as a storage pool for circulating S1P, platelets can rapidly generate S1P de novo, store it in large quantities, and release it when the platelet is activated. Platelets can thus provide S1P in a short time when needed or in the case of an injury with subsequent platelet activation and thereby regulate local cellular responses. In addition, platelet-dependently generated and released S1P may also influence long-term immune cell functions in various disease processes, such as inflammation-driven vascular diseases. In this review, the metabolism and release of platelet S1P are presented, and the autocrine versus paracrine functions of platelet-derived S1P and its relevance in various disease processes are discussed. New pharmacological approaches that target the auto- or paracrine effects of S1P may be therapeutically helpful in the future for pathological processes involving S1P.
鞘氨醇-1-磷酸（S1P）是一种多功能信号脂质，参与多种细胞过程的调节。S1P 调节细胞增殖、迁移和凋亡以及免疫细胞的功能。S1P 由鞘氨醇（Sph）生成，后者来自神经酰胺代谢。特别是，血液中存在高浓度的 S1P。这主要来源于红细胞、内皮细胞（EC）和血小板。虽然红细胞是循环 S1P 的储存池，但血小板可以迅速从头合成 S1P，大量储存并在血小板激活时释放。因此，当需要时或在血小板激活和随后的局部细胞反应的情况下发生损伤时，血小板可以在短时间内提供 S1P。此外，血小板依赖性生成和释放的 S1P 也可能影响各种疾病过程中的长期免疫细胞功能，例如炎症驱动的血管疾病。在这篇综述中，介绍了血小板 S1P 的代谢和释放，讨论了血小板衍生的 S1P 的自分泌和旁分泌功能及其在各种疾病过程中的相关性。针对 S1P 的自分泌或旁分泌作用的新的药理学方法可能在未来涉及 S1P 的病理过程中具有治疗意义。
