E-Cigarette Exposure Decreases Bone Marrow Hematopoietic Progenitor Cells

E-Cigarette Exposure Decreases Bone Marrow Hematopoietic Progenitor Cells
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DOI:
10.3390/cancers12082292
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发表时间:
2020-08-01
期刊:
影响因子:
5.2
通讯作者:
Fleischman, Angela G.
Fleischman, Angela G.
中科院分区:
医学2区
文献类型:
--
作者:
Ramanathan, Gajalakshmi;Craver-Hoover, Brianna;Fleischman, Angela G.

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电子烟(E-cigs)产生含有尼古丁的气雾剂供吸入,已成为青少年和年轻人中的一种受欢迎的烟草产品,但由于相对较新的引入,人们对其健康影响知之甚少。很少有研究评估吸入电子烟烟雾或蒸气的长期影响。在这里,我们证明了两个月的电子烟暴露会导致骨髓造血干细胞和祖细胞(HSPC)的抑制。具体地说,与空气暴露的小鼠相比,暴露于E-CIG的动物中常见的髓系祖细胞和粒细胞-巨噬细胞前体细胞减少。两个月的E-CIG暴露对骨髓移植中的竞争性重建没有影响。当空气和E-CIG暴露的小鼠受到内毒素(LPS)炎症刺激时,两组之间的竞争适合度没有显著差异。然而,接受电子烟加脂多糖暴露的小鼠骨髓移植的小鼠在移植后5个月外周血中单核细胞水平升高,表明有髓系倾向,类似于老化的造血干细胞(HSC)对急性炎症挑战的反应。我们还研究了电子烟暴露是否增强了具有髓系恶性肿瘤相关突变的造血细胞的选择性优势。电子烟暴露1个月后,外周血中JAK2(V617F)突变细胞略有增加,但对TET2(-/-)细胞无影响。综上所述,我们的研究结果显示,两个月的慢性电子烟暴露改变了骨髓HSPC群体,但不影响初次移植中HSC的重建。
Electronic cigarettes (E-cigs) generate nicotine containing aerosols for inhalation and have emerged as a popular tobacco product among adolescents and young adults, yet little is known about their health effects due to their relatively recent introduction. Few studies have assessed the long-term effects of inhaling E-cigarette smoke or vapor. Here, we show that two months of E-cigarette exposure causes suppression of bone marrow hematopoietic stem and progenitor cells (HSPCs). Specifically, the common myeloid progenitors and granulocyte-macrophage progenitors were decreased in E-cig exposed animals compared to air exposed mice. Competitive reconstitution in bone marrow transplants was not affected by two months of E-cig exposure. When air and E-cig exposed mice were challenged with an inflammatory stimulus using lipopolysaccharide (LPS), competitive fitness between the two groups was not significantly different. However, mice transplanted with bone marrow from E-cigarette plus LPS exposed mice had elevated monocytes in their peripheral blood at five months post-transplant indicating a myeloid bias similar to responses of aged hematopoietic stem cells (HSC) to an acute inflammatory challenge. We also investigated whether E-cigarette exposure enhances the selective advantage of hematopoietic cells with myeloid malignancy associated mutations. E-cigarette exposure for one month slightly increasedJAK2(V617F)mutant cells in peripheral blood but did not have an impact onTET2(-/-)cells. Altogether, our findings reveal that chronic E-cigarette exposure for two months alters the bone marrow HSPC populations but does not affect HSC reconstitution in primary transplants.