Erythrocyte-derived sphingosine 1-phosphate is essential for vascular development.
Erythrocyte-derived sphingosine 1-phosphate is essential for vascular development.
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DOI：
10.1172/jci77685
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发表时间：
2014-11
期刊：
影响因子：
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通讯作者：
Yuquan Xiong;Peiying Yang;R. Proia;T. Hla
中科院分区：
文献类型：
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作者：
Yuquan Xiong;Peiying Yang;R. Proia;T. Hla
红细胞（rbc）的氧气运输对生命和胚胎发育至关重要。在这里，我们确定，提供脂质介质鞘氨醇1-磷酸（S1 P）的体循环是一个必不可少的功能，红细胞在胚胎发生。rbc特异性缺失鞘氨醇激酶1和2（Sphk 1和Sphk 2）的小鼠在E11.5和E12.5之间表现出胚胎致死性，这是由于血管发育缺陷。给妊娠母鼠施用S1 P1受体激动剂可挽救早期胚胎致死率。尽管rbc特异性Sphk 1 Sphk 2-KO胚胎贫血，但造血干细胞（HSC）的红细胞生成能力并未受损，这表明rbc可以在缺乏鞘氨醇激酶活性的情况下发育。事实上，将Sphk 1和Sphk 2缺陷的HSC移植到成年小鼠中产生了缺乏S1 P的红细胞，并减弱了受体血浆S1 P水平。然而，在成年动物中，红细胞和内皮细胞都有助于血浆S1 P。总之，这些研究结果表明，红细胞是必不可少的胚胎发育提供溶血磷脂S1 P，通过其受体调节胚胎血管发育。
Transport of oxygen by red blood cells (rbc) is critical for life and embryogenesis. Here, we determined that provision of the lipid mediator sphingosine 1-phosphate (S1P) to the systemic circulation is an essential function of rbc in embryogenesis. Mice with rbc-specific deletion of sphingosine kinases 1 and 2 (Sphk1 and Sphk2) showed embryonic lethality between E11.5 and E12.5 due to defects in vascular development. Administration of an S1P1 receptor agonist to pregnant dams rescued early embryonic lethality. Even though rbc-specific Sphk1 Sphk2-KO embryos were anemic, the erythropoietic capacity of hematopoietic stem cells (HSCs) was not impaired, suggesting that rbc can develop in the absence of sphingosine kinase activity. Indeed, transplantation of HSCs deficient for Sphk1 and Sphk2 into adult mice produced rbc that lacked S1P and attenuated plasma S1P levels in recipients. However, in adult animals, both rbc and endothelium contributed to plasma S1P. Together, these findings demonstrate that rbc are essential for embryogenesis by supplying the lysophospholipid S1P, which regulates embryonic vascular development via its receptors.