Mairbäurl Heimo
Medical Clinic VII, Sports Medicine, Translational Lung Research Center, German Center for Lung Research, University Hospital Heidelberg, Heidelberg, Germany.
Front Physiol. 2018 Apr 5;9:345. doi: 10.3389/fphys.2018.00345. eCollection 2018.
Neocytolysis is the selective destruction of those erythrocytes that had been formed during stress-erythropoiesis in hypoxia in order to increase the oxygen transport capacity of blood. Neocytolysis likely aims at decreasing this excess amount of erythrocytes and hemoglobin (Hb) when it is not required anymore and to decrease blood viscosity. Neocytolysis seems to occur upon descent from high altitude. Similar processes seem to occur in microgravity, and are also discussed to mediate the replacement of erythrocytes containing fetal hemoglobin (HbF) with those having adult hemoglobin (HbA) after birth. This review will focus on hypoxia at high altitude. Hemoglobin concentration and total hemoglobin in blood increase by 20-50% depending on the altitude (i.e., the degree of hypoxia) and the duration of the sojourn. Upon return to normoxia hemoglobin concentration, hematocrit, and reticulocyte counts decrease faster than expected from inhibition of stress-erythropoiesis and normal erythrocyte destruction rates. In parallel, an increase in haptoglobin, bilirubin, and ferritin is observed, which serve as indirect markers of hemolysis and hemoglobin-breakdown. At the same time markers of progressing erythrocyte senescence appear even on reticulocytes. Unexpectedly, reticulocytes from hypoxic mice show decreased levels of the hypoxia-inducible factor HIF-1α and decreased activity of the BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), which results in elevated mitochondrial activity in these cells. Furthermore, hypoxia increases the expression of miR-21, which inhibits the expression of catalase and thus decreases one of the most important mechanisms protecting against oxygen free radicals in erythrocytes. This unleashes a series of events which likely explain neocytolysis, because upon re-oxygenation systemic and mitochondrial oxygen radical formation increases and causes the selective destruction of those erythrocytes having impaired anti-oxidant capacity.
新细胞溶解是对那些在缺氧应激性红细胞生成过程中形成的红细胞进行选择性破坏，以提高血液的氧运输能力。当不再需要过量的红细胞和血红蛋白（Hb）时，新细胞溶解可能旨在减少其数量，并降低血液粘度。新细胞溶解似乎发生在从高海拔下降时。类似的过程似乎也发生在微重力环境中，并且也有人讨论其在出生后介导含有胎儿血红蛋白（HbF）的红细胞被含有成人血红蛋白（HbA）的红细胞替代的过程。本综述将聚焦于高海拔地区的缺氧情况。血液中的血红蛋白浓度和总血红蛋白量会根据海拔高度（即缺氧程度）和停留时间增加20%-50%。回到常氧状态后，血红蛋白浓度、血细胞比容和网织红细胞计数的下降速度比应激性红细胞生成受抑制和正常红细胞破坏率所预期的要快。同时，观察到触珠蛋白、胆红素和铁蛋白增加，它们作为溶血和血红蛋白分解的间接标志物。与此同时，即使在网织红细胞上也出现了红细胞衰老进展的标志物。出乎意料的是，来自缺氧小鼠的网织红细胞显示缺氧诱导因子HIF-1α水平降低，以及BCL2/腺病毒E1B 19 kDa蛋白相互作用蛋白3（BNIP3）的活性降低，这导致这些细胞中线粒体活性升高。此外，缺氧会增加miR-21的表达，miR-21会抑制过氧化氢酶的表达，从而降低红细胞中最重要的抗氧化机制之一。这引发了一系列事件，这些事件可能解释了新细胞溶解现象，因为在再给氧时，全身和线粒体氧自由基的形成增加，并导致那些抗氧化能力受损的红细胞被选择性破坏。
