Department of Experimental Physics, University Campus, Building E2.6, Saarland University, 66123 Saarbrücken, Germany.
Department of Experimental Surgery, Campus University Hospital, Building 65, Saarland University, 66421 Homburg, Germany.
Cells. 2022 Mar 23;11(7):1082. doi: 10.3390/cells11071082.
Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. At high altitude, EPO levels first increase and then decrease, although erythropoiesis remains elevated at a stable level. The roles of hypoxia and related EPO adjustments are not fully understood, which has contributed to the formulation of the theory of neocytolysis. We aimed to evaluate the role of oxygen exclusively on erythropoiesis, comparing in vitro erythroid differentiation performed at atmospheric oxygen, a lower oxygen concentration (three percent oxygen) and with cultures of erythroid precursors isolated from peripheral blood after a 19-day sojourn at high altitude (3450 m). Results highlight an accelerated erythroid maturation at low oxygen and more concave morphology of reticulocytes. No differences in deformability were observed in the formed reticulocytes in the tested conditions. Moreover, hematopoietic stem and progenitor cells isolated from blood affected by hypoxia at high altitude did not result in different erythroid development, suggesting no retention of a high-altitude signature but rather an immediate adaptation to oxygen concentration. This adaptation was observed during in vitro erythropoiesis at three percent oxygen by a significantly increased glycolytic metabolic profile. These hypoxia-induced effects on in vitro erythropoiesis fail to provide an intrinsic explanation of the concept of neocytolysis.
缺氧会导致促红细胞生成素（EPO）释放增加，从而促进红细胞生成。在高海拔地区，EPO 水平先升高后降低，尽管红细胞生成仍保持在稳定水平。缺氧和相关 EPO 调节的作用尚未完全阐明，这促成了新生细胞溶解理论的提出。我们旨在评估氧气对红细胞生成的单独作用，比较在大气氧、低氧浓度（3%氧）下以及在高海拔（3450 米）停留 19 天后从外周血分离的红细胞前体细胞培养物中进行的体外红细胞分化。结果突出显示低氧条件下红细胞成熟加速，网织红细胞形态更凹。在测试条件下，形成的网织红细胞的变形性没有差异。此外，从高海拔缺氧影响的血液中分离出的造血干细胞和祖细胞并未导致不同的红细胞发育，这表明没有保留高海拔特征，而是对氧浓度的即时适应。这种适应在 3%氧的体外红细胞生成中通过显著增加的糖酵解代谢谱观察到。这些缺氧对体外红细胞生成的影响不能为新生细胞溶解的概念提供内在解释。
