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. 2020 Aug 14;12(8):2292.
doi: 10.3390/cancers12082292.

E-Cigarette Exposure Decreases Bone Marrow Hematopoietic Progenitor Cells

Gajalakshmi Ramanathan  1 , Brianna Craver-Hoover  2 , Rebecca J Arechavala  3 , David A Herman  3 , Jane H Chen  2 , Hew Yeng Lai  2 , Samantha R Renusch  3 , Michael T Kleinman  3 , Angela G Fleischman  1   2
Affiliations

E-Cigarette Exposure Decreases Bone Marrow Hematopoietic Progenitor Cells

Gajalakshmi Ramanathan et al. Cancers (Basel). .

Abstract

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 increased JAK2V617F mutant cells in peripheral blood but did not have an impact on TET2-/- 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.

Keywords: electronic cigarette; hematopoietic stem cell; lipopolysaccharide; myeloid progenitors; myeloproliferative neoplasm.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number T32CA009054. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Figures

Figure 1
Figure 1
Two-month E-cigarette exposure does not affect peripheral blood cell counts of (A) red blood cells, (B) platelets, (C) leukocytes, and (D) leukocyte differentials in C57Bl/6J mice. (E) Bone marrow cellularity, (F) lineage positive cells, and (G) spleen weight after E-cigarette exposure in air and E-cigarette exposed mice. Data are shown as mean ± SEM, n = 4–7 mice/group. WBC, white blood cell; BMCs, bone marrow cells; Lin+, lineage positive.
Figure 2
Figure 2
E-cigarette exposure suppresses myeloid progenitor cell numbers in the bone marrow. (A) Gating scheme for the characterization of progenitor cell sub-types. Absolute numbers of (B) lineage- (Lin-), (C) lineage-, c-Kit+ (LK) and (D) CMP, GMP and MEP per femur. Data are shown as mean ± SEM, n = 4 mice/group. * p < 0.05, ** p < 0.01, unpaired student’s t-test.
Figure 3
Figure 3
E-cigarette exposure suppresses HSPC numbers in the bone marrow. (A) Gating scheme for the characterization of HSPC sub-types. Absolute numbers of (B) LKS and (C) LKS-SLAM populations per femur. Data are shown as mean ± SEM, n = 4 mice/group. p-value determined by unpaired student’s t-test.
Figure 4
Figure 4
HSC function is unperturbed following E-cigarette exposure. (A) Competitive transplant set-up and peripheral blood (PB) chimerism analysis. (B) PB chimerism of CD45.2 leukocytes post- transplant. Peripheral blood cell counts of (C) leukocytes, (D) red blood cells and (E) platelets at 20 weeks post-transplant. Data are shown as mean ± SEM, n = 5–6 mice/group. BM, bone marrow.
Figure 5
Figure 5
Systemic LPS post-E-cigarette exposure results in persistent monocytosis. (A) Experimental design. (B) Peripheral blood chimerism of CD45.2 leukocytes from air and E-cigarette exposed donor cells. Peripheral blood counts of (C) CD45.2 monocytes, (D) leukocytes, (E) CD45.2 leukocytes, (F) red blood cells, and (G) platelets 20 weeks post-transplant. Data are shown as mean ± SEM. n = 5–6 mice/group. * p < 0.05, unpaired student’s t-test.
Figure 6
Figure 6
E-cigarette exposure increases peripheral blood chimerism of JAK2V617F mutant cells. (A) Experimental design. Relative change in peripheral blood chimerism of (B) JAK2V617F mutant and (C) TET2−/− cells from pre-exposure. (D) Relative contribution of JAK2V617F to HSPC populations after 2 months of exposure. Data are shown as mean ± SEM. n = 5–10 mice/group.
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