Oxygen tension influences the differentiation, maturation and apoptosis of human megakaryocytes
Oxygen tension influences the differentiation, maturation and apoptosis of human megakaryocytes
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DOI：
10.1046/j.1365-2141.2000.02457.x
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发表时间：
2000-12-01
影响因子：
6.5
通讯作者：
Papoutsakis, ET
中科院分区：
文献类型：
--
作者：
Mostafa, SS;Miller, WM;Papoutsakis, ET
巨核细胞 (Mks) 在骨髓 (BM) 窦壁附近成熟，随后在窦腔或肺毛细血管内释放血小板。由于血小板释放部位的氧张力 (pO(2)) 水平高于干细胞和祖细胞所在的 BM 核心，因此我们研究了 pO(2) 是否影响 Mk 成熟。 Mks 是由 CD34(+) 细胞（来自癌症患者的动员外周血）在 5% 和 20% O-2 下生成的。第15天时，20%和5% O-2培养物中的CD41(+) Mk扩增分别为85倍和31倍。 20% 的 O-2 培养物还具有更高水平的高倍性（大于或等于 8N，高八倍）和前血小板形成（高五倍）Mks。第 21 天时，20% O-2 培养物的凋亡 Mks 数量增加了五倍。相反，5% O-2 促进 Mk 集落形成单位 (CFU-Mk) 的生成和维持。在用 CD41(+) Mks 启动的培养物中观察到类似的结果，表明 pO(2) 直接影响 Mks。第 5 天和第 7 天从 20% 到 5% O-2 的变化延迟了成熟和细胞凋亡，表明这两个过程密切相关。这些结果在正常骨髓样本的 CD34(+) 培养物中得到证实。这些数据可以提供对体内 Mk 成熟的见解，例如对动物缺氧诱导的血小板减少症的解释。
Megakaryocytes (Mks) mature adjacent to bone marrow (BM) sinus walls and subsequently release platelets within the sinusoidal space or in lung capillaries. As the sites for platelet release have higher levels of oxygen tension (pO(2)) than the core of the BM where stem and progenitor cells reside, we investigated whether pO(2) influences Mk maturation. Mks were generated from CD34(+) cells (from mobilized peripheral blood from cancer patients) under 5% and 20% O-2. At day 15, CD41(+) Mk expansion in 20% and 5% O-2 cultures was 85-fold and 31-fold respectively. Twenty percent O-2 cultures also had higher levels of high ploidy (greater than or equal to 8N, eightfold higher) and proplatelet-forming (fivefold higher) Mks. At day 21, 20% O-2 cultures had a fivefold higher number of apoptotic Mks. In contrast, 5% O-2 promoted Mk colony-forming unit (CFU-Mk) generation and maintenance. Similar results were observed in cultures initiated with CD41(+) Mks, indicating that pO(2) directly affects Mks. The change from 20% to 5% O-2 on day 5 and day 7 delayed both maturation and apoptosis, suggesting that these two processes are closely linked. These results were confirmed in CD34(+) cultures from normal BM samples. These data may provide insights into in vivo Mk maturation, such as an explanation for hypoxia-induced thrombocytopenia in animals.