Red blood cells express a functional endothelial nitric oxide synthase
Red blood cells express a functional endothelial nitric oxide synthase
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DOI：
10.1182/blood-2005-10-3992
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发表时间：
2006-04-01
期刊：
影响因子：
20.3
通讯作者：
Kelm, M
中科院分区：
文献类型：
--
作者：
Kleinbongard, P;Schulz, R;Kelm, M
循环中一氧化氮（NO）的合成完全归因于血管内皮细胞。红细胞 (RBC) 已被证明携带无功能的一氧化氮合酶 (NOS)，并且由于其血红蛋白含量很高，因此被认为可以代谢大量的一氧化氮。然而，最近，红细胞已被证实可以在心血管系统内可逆地结合、转运和释放 NO。我们现在提供的证据表明，人类红细胞表达活性和功能性内皮型一氧化氮合酶（eNOS），它位于红细胞的质膜和细胞质中。该 NOS 受其底物 L-精氨酸、钙以及 PI3 激酶磷酸化的调节。 RBC-NOS 活性调节红细胞膜的变形性并抑制血小板的活化。红细胞中 L-精氨酸的 NOS 依赖性转化与培养的人内皮细胞相当。与野生型小鼠相比，eNOS(-/-) 小鼠的红细胞缺乏 NOS 蛋白和活性，这强化了红细胞中存在 eNOS 的证据。这些数据显示红细胞中的类 eNOS 蛋白和活性在红细胞和血小板中发挥调节功能，这可能会激发治疗几种血管和血液疾病固有的 NO 缺乏状态的新方法。
The synthesis of nitric oxide (NO) in the circulation has been attributed exclusively to the vascular endothelium. Red blood cells (RBCs) have been demonstrated to carry a nonfunctional NO synthase (NOS) and, due to their huge hemoglobin content, have been assumed to metabolize large quantities of NO. More recently, however, RBCs have been identified to reversibly bind, transport, and release NO within the cardiovascular system. We now provide evidence that RBCs from humans express an active and functional endothelial-type NOS (eNOS), which is localized in the plasma membrane and the cytoplasm of RBCs. This NOS is regulated by its substrate L-arginine, by calcium, and by phosphorylation via PI3 kinase. RBC-NOS activity regulates deformability of RBC membrane and inhibits activation of platelets. The NOS-dependent conversion Of L-arginine in RBCs is comparable to that of cultured human endothelial cells. RBCs in eNOS(-/-) mice in contrast to wild-type mice lack NOS protein and activity, strengthening the evidence of an eNOS in RBCs. These data show an eNOS-like protein and activity in RBCs serving regulatory functions in RBCs and platelets, which may stimulate new approaches in the treatment of NO deficiency states inherent to several vascular and hematologic diseases.