Bradford M Kuhlman, Jonathan H Diaz, Trang Simon, Kimberly D Reeves, Stephen J Walker, Anthony Atala, Graça Almeida-Porada, Christopher D Porada
{"title":"模拟微重力会损害人类 NK 细胞对太空辐射相关白血病细胞的细胞毒活性。","authors":"Bradford M Kuhlman, Jonathan H Diaz, Trang Simon, Kimberly D Reeves, Stephen J Walker, Anthony Atala, Graça Almeida-Porada, Christopher D Porada","doi":"10.1038/s41526-024-00424-1","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54263,"journal":{"name":"npj Microgravity","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324864/pdf/","citationCount":"0","resultStr":"{\"title\":\"Simulated microgravity impairs human NK cell cytotoxic activity against space radiation-relevant leukemic cells.\",\"authors\":\"Bradford M Kuhlman, Jonathan H Diaz, Trang Simon, Kimberly D Reeves, Stephen J Walker, Anthony Atala, Graça Almeida-Porada, Christopher D Porada\",\"doi\":\"10.1038/s41526-024-00424-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":54263,\"journal\":{\"name\":\"npj Microgravity\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-08-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324864/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"npj Microgravity\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1038/s41526-024-00424-1\",\"RegionNum\":1,\"RegionCategory\":\"物理与天体物理\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj Microgravity","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/s41526-024-00424-1","RegionNum":1,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
自然杀伤(NK)细胞是抵御恶性细胞的重要第一道防线。由于宇航员暴露在太空辐射中可能会增加患癌风险,我们研究了太空飞行中的微重力是否会影响人体对白血病发生的防御能力。在正常重力和模拟微重力(sμG)条件下培养人类 NK 细胞 48 小时,并使用标准方法或在持续的 sμG 条件下测量其对 K-562(CML)和 MOLT-4(T-ALL)细胞的细胞毒性。这种短暂的 sμG 暴露明显降低了 NK 对这两种白血病的细胞毒性,而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-seq 分析有助于深入了解 sμG 降低细胞毒性的机制。鉴于我们之前关于太空辐射诱导人体体内 T-ALL 的报告,针对 MOLT-4 的细胞毒性降低令人震惊,并提出了一种可能性,即在低地轨道以外的长期任务中,μG 可能会增加宇航员白血病发生的风险。
Simulated microgravity impairs human NK cell cytotoxic activity against space radiation-relevant leukemic cells.
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.
npj MicrogravityPhysics and Astronomy-Physics and Astronomy (miscellaneous)
CiteScore
7.30
自引率
7.80%
发文量
50
审稿时长
9 weeks
期刊介绍:
A new open access, online-only, multidisciplinary research journal, npj Microgravity is dedicated to publishing the most important scientific advances in the life sciences, physical sciences, and engineering fields that are facilitated by spaceflight and analogue platforms.