Kumar A, Saba J D
Department of Biochemistry, All India Institute of Medical Sciences [AIIMS], Saket Nagar, Bhopal 462 020, India.
Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, California 94609, USA.
Cell Mol Biol (OMICS). 2015;61(2). Epub 2015 Dec 31.
Sphingosine-1-phosphate [S1P] is a potent bioactive sphingolipid molecule. In response to a stimulus, S1P is produced intracellularly by the action of two sphingosine kinases, and then it is exported to the extracellular environment or acts as an intracellular second messenger. S1P binds to its cognate G-protein coupled receptors, which are known as S1P receptors. There are five S1P receptors that have been identified in vertebrates. By activating S1P receptors, S1P controls a variety of physiological and pathological processes including cell migration, angiogenesis, vascular maturation, inflammation, and invasion, metastasis, and chemoresistance in cancer. S1P has emerged as a critical regulator of leukocyte migration and plays a central role in lymphocyte egress from the thymus and secondary lymphoid organs. In the current review article, we summarize the current understanding of the emigration of lymphocytes and other leukocytes from bone marrow, thymus and secondary lymphoid organs to the circulation, as well as the clinical implications of modulating the activity of the major S1P receptor, S1PR1.
1-磷酸鞘氨醇[S1P]是一种强效的生物活性鞘脂分子。在受到刺激时，S1P通过两种鞘氨醇激酶的作用在细胞内产生，然后被转运到细胞外环境或作为细胞内第二信使发挥作用。S1P与其同源的G蛋白偶联受体结合，这些受体被称为S1P受体。在脊椎动物中已鉴定出五种S1P受体。通过激活S1P受体，S1P控制多种生理和病理过程，包括细胞迁移、血管生成、血管成熟、炎症以及癌症中的侵袭、转移和化疗耐药性。S1P已成为白细胞迁移的关键调节因子，并在淋巴细胞从胸腺和二级淋巴器官逸出中起核心作用。在当前的综述文章中，我们总结了目前对淋巴细胞和其他白细胞从骨髓、胸腺和二级淋巴器官迁移到循环系统的理解，以及调节主要S1P受体S1PR1活性的临床意义。
