Kuhlman Bradford M, Diaz Jonathan H, Simon Trang, Reeves Kimberly D, Walker Stephen J, Atala Anthony, Almeida-Porada Graça, Porada Christopher D
Wake Forest Institute for Regenerative Medicine, Winston Salem, NC, USA.
Wake Forest Center for Precision Medicine, Winston Salem, NC, USA.
NPJ Microgravity. 2024 Aug 14;10(1):85. doi: 10.1038/s41526-024-00424-1.
Natural killer (NK) cells are an important first-line of defense against malignant cells. Because of the potential for increased cancer risk from astronaut exposure to space radiation, we determined whether microgravity present during spaceflight affects the body's defenses against leukemogenesis. Human NK cells were cultured for 48 h under normal gravity and simulated microgravity (sμG), and cytotoxicity against K-562 (CML) and MOLT-4 (T-ALL) cells was measured using standard methodology or under continuous sμG. This brief exposure to sμG markedly reduced NK cytotoxicity against both leukemias, and these deleterious effects were more pronounced in continuous sμG. RNA-seq performed on NK cells from two additional healthy donors provided insight into the mechanism(s) by which sμG reduced cytotoxicity. Given our prior report of space radiation-induced human T-ALL in vivo, the reduced cytotoxicity against MOLT-4 is striking and raises the possibility that μG may increase astronaut risk of leukemogenesis during prolonged missions beyond LEO.
自然杀伤（NK）细胞是抵御恶性细胞的重要第一道防线。由于宇航员暴露于太空辐射中存在癌症风险增加的可能性，我们确定了太空飞行期间存在的微重力是否会影响机体对白血病发生的防御。将人NK细胞在正常重力和模拟微重力（sμG）条件下培养48小时，并使用标准方法或在连续sμG条件下测量其对K-562（慢性粒细胞白血病）和MOLT-4（T细胞急性淋巴细胞白血病）细胞的细胞毒性。这种对sμG的短暂暴露显著降低了NK细胞对两种白血病细胞的细胞毒性，并且这些有害影响在连续sμG条件下更为明显。对另外两名健康供体的NK细胞进行的RNA测序揭示了sμG降低细胞毒性的机制。鉴于我们之前关于太空辐射在体内诱导人T细胞急性淋巴细胞白血病的报告，对MOLT-4细胞毒性的降低令人震惊，并增加了微重力可能在近地轨道以外的长期任务期间增加宇航员白血病发生风险的可能性。
