Erythrocytes Serve as a Reservoir for Cellular and Extracellular Sphingosine 1-Phosphate
Erythrocytes Serve as a Reservoir for Cellular and Extracellular Sphingosine 1-Phosphate
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DOI：
10.1002/jcb.22507
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发表时间：
2010-04-15
影响因子：
4
通讯作者：
Graeler, Markus H.
中科院分区：
文献类型：
--
作者：
Bode, Constantin;Sensken, Sven-Christian;Graeler, Markus H.
血液中的鞘氨醇1-磷酸（S1P）通过红细胞磷酸化、储存和运输。S1P从红细胞释放到血浆是一个受调节的过程，在无血浆或无血清的培养基中不会发生。血浆分离和分离蛋白和重组蛋白孵育发现，高密度脂蛋白（HDL）和血清白蛋白（SA）是红细胞释放S1P的非冗余内源性触发因子。在钙通量实验中，S1P结合SA和HDL能够刺激S1P(1)受体。正如抗S1P抗体Sphingomab （TM）所证明的那样，受体分子的结合能力触发S1P的释放。HDL比SA从红细胞膜中提取更多的S1P。来自贫血患者的血液样本证实血浆中S1P释放能力降低。在红细胞和内皮细胞（EC）的共培养中，我们观察到S1P的跨细胞转运是红细胞相关S1P在缺乏SA和HDL以及红细胞-EC紧密接触时的第二个功能，模拟了组织间质和毛细血管中的情况。与S1P结合SA和HDL相反，S1P裂解酶（SGPL1）抑制后，红细胞相关的S1P被EC显著结合。因此，红细胞相关的S1P有两个功能：(1)它有助于SGPL1敏感的S1P在组织中跨细胞运输后的细胞池；(2)它通过SA和HDL帮助维持细胞外S1P水平，独立于SGPL1活性。j .细胞。中国生物医学工程学报，2009,31(2):393 - 393。(C) 2010 Wiley-Liss, Inc。
Sphingosine 1-phosphate (S1P) in blood is phosphorylated, stored, and transported by red blood cells (RBC). Release of S1P from RBC into plasma is a regulated process that does not occur in plasma- or serum-free media. Plasma fractionation and incubations with isolated and recombinant proteins identified high density lipoprotein (HDL) and serum albumin (SA) as non-redundant endogenous triggers for S1P release from RBC. S1P bound to SA and HDL was able to stimulate the S1P(1) receptor in calcium flux experiments. The binding capability of acceptor molecules triggers S1P release, as demonstrated with the anti-S1P antibody Sphingomab (TM). More S1P was extracted from RBC membranes by HDL than by SA. Blood samples from anemic patients confirmed a reduced capacity for S1P release in plasma. In co-cultures of RBC and endothelial cells (EC), we observed transcellular transportation of S1P as a second function of RBC-associated S1P in the absence of SA and HDL and during tight RBC-EC contact, mimicking conditions in tissue interstitium and capillaries. In contrast to S1P bound to SA and HDL, RBC-associated S1P was significantly incorporated by EC after S1P lyase (SGPL1) inhibition. RBC-associated S1P, therefore, has two functions: (1) It contributes to the cellular pool of SGPL1-sensitive S1P in tissues after transcellular transportation and (2) it helps maintain extracellular S1P levels via SA and HDL independently from SGPL1 activity. J. Cell. Biochem. 109: 1232-1243, 2010. (C) 2010 Wiley-Liss, Inc.