Absence of neocytolysis in humans returning from a 3-week high-altitude sojourn
Absence of neocytolysis in humans returning from a 3-week high-altitude sojourn
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DOI：
10.1111/apha.13647
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发表时间：
2021-03-17
影响因子：
6.3
通讯作者：
Mairbaeurl, Heimo
中科院分区：
文献类型：
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作者：
Klein, Marie;Kaestner, Lars;Mairbaeurl, Heimo
目的：总血红蛋白质量(TOT-Hb)在高原习服过程中升高。下降时TOT-Hb的正常化被认为是通过新细胞溶解发生的，新形成的红细胞被选择性地破坏。由于缺乏令人信服的新细胞溶解的实验证据，我们进行了一项关于在Jungfraujoch Research Station(JFJRS；3450m)停留后红细胞存活的前瞻性研究。方法：12名男性受试者(平均年龄23.3岁)的新形成的红细胞分别在常氧(110m)和19天的高原停留期间被标记为(13)C2和N-15标记的甘氨酸。采用血红素同位素比值质谱仪，通过测定TOT-Hb、网织红细胞计数、红细胞膜蛋白4.1a/4.1b比值和数学模型，测定常氧和高原条件下红细胞的清除动力学。结果：TOT-Hb在高海拔地区升高了4.7%+/-2.7%，在下降后11天内恢复到海拔前水平。C-13-(常氧)和N-15-(高原)标记红细胞的清除没有差别。红细胞生成素水平和CD71阳性网织红细胞计数在下降后迅速下降。4.1a/4.1b比值在海拔高度呈下降趋势，下降后3~4d仍维持在较低水平，并缓慢恢复正常。没有溶血的迹象。结论：我们证实TOT-Hb在下降时迅速正常化。根据高海拔地区标记的红细胞的年龄队列没有加速移除、网织红细胞计数和4.1a/4.1b带比率的变化模式以及模型，这种下降不是通过新细胞溶解而发生的，而是由于红细胞生成率降低以及衰老红细胞的正常清除所致。
Aims: Total haemoglobin mass (tot-Hb) increases during high-altitude acclimatization. Normalization of tot-Hb upon descent is thought to occur via neocytolysis, the selective destruction of newly formed erythrocytes. Because convincing experimental proof of neocytolysis is lacking, we performed a prospective study on erythrocyte survival after a stay at the Jungfraujoch Research Station (JFJRS; 3450 m).Methods: Newly formed erythrocytes of 12 male subjects (mean age 23.3 years) were age cohort labelled in normoxia (110 m) and during a 19-day high-altitude sojourn by ingestion of (13)C2- and N-15-labelled glycine respectively. Elimination dynamics for erythrocytes produced in normoxia and at high altitude were measured by isotope ratio mass spectrometry of haem, by determining tot-Hb, reticulocyte counts, erythrocyte membrane protein 4.1a/4.1b ratio and by mathematical modelling.Results: Tot-Hb increased by 4.7% +/- 2.7% at high altitude and returned to pre-altitude values within 11 days after descent. Elimination of C-13-(normoxia) and N-15-(high altitude) labelled erythrocytes was not different. Erythropoietin levels and counts of CD71-positive reticulocytes decreased rapidly after descent. The band 4.1a/4.1b ratio decreased at altitude and remained low for 3-4 days after descent and normalized slowly. There was no indication of haemolysis.Conclusion: We confirm a rapid normalization of tot-Hb upon descent. Based on the lack of accelerated removal of age cohorts of erythrocytes labelled at high altitude, on patterns of changes in reticulocyte counts and of the band 4.1a/4.1b ratio and on modelling, this decrease did not occur via neocytolysis, but by a reduced rate of erythropoiesis along with normal clearance of senescent erythrocytes.