Cholinergic activation of hematopoietic stem cells: role in tobacco-related disease?

Abstract

Rationale Tobacco use is associated with an increase in white blood cell count (WBC). This association has been attributed to bronchopulmonary inflammation and/or infection. It is not known if nicotine itself may play a role. Objectives We determined if nicotine itself could effect WBC count, and determined if this was due to a direct effect on hematopoietic stem cells (HSC). Methods and Measurements C57Bl6J mice received nicotine orally, and measurements of WBC count; bone marrow and spleen cellularity; and HSC count were made. To determine the functionality of HSCs, irradiated animals received bone marrow transplants from vehicle or nicotine treated mice. Main Results Nicotine increased leukocytes in the peripheral blood, bone marrow and spleen. Peripheral red cell and platelet count were unaffected. Nicotine increased the frequency of HSC in the bone marrow. Isolated long-term HSCs from nicotine-treated mice transplanted into irradiated mice regenerated all hematopoeitic cell lineages, demonstrating functional competence of those HSCs. HSC expressed nicotinic acetylcholine receptors (nAChRs), as documented by FITC-conjugated alpha-bungarotoxin binding. Nicotine increased soluble Kit ligand, consistent with stem cell activation. Conclusions The data suggest a new mechanism for the increased WBC associated with tobacco use. The effect of nicotine to activate hematopoiesis may contribute to tobacco-related diseases.

Exposure to Nicotine Adversely Affects the Dendritic Cell System and Compromises Host Response to Vaccination

“…We also examined whether DCs isolated from nicotine-exposed mice have the capability to prime Ag-specific immune responses ex vivo. Although we found an increase in the total number of splenocytes recovered from nicotine-exposed mice compared with control mice as previously reported (30) (Fig. 5F), our data suggest no significant differences in the frequency and absolute numbers of total splenic CD11c + MHC II + DCs (Fig.…”

Effect of Sub-Lethal Doses of Smokeless Tobacco (Snuff) on Some Haemato-Rheological Parameters Using Albino Wistar Rats

“…Furthermore, the blood of tobacco smokers and snuffers is reported to contain significant concentration of nicotine [14]. Nicotine is known to cause the release of adrenalin and increases leukocytes in the peripheral blood, bone marrow and spleen [13]. The increase in WBC count in this study may also be attributed to increase in nicotine at higher doses of tobacco snuff, and subsequent release of adrenalin which mobilizes the leucocytes marginated in the blood capillaries.…”

“…Tobacco use is associated with an increase in the white blood cell count. This association has been attributed to bronchopulmonary inflammation and/or infection [13]. Increased WBC counts in the present study may suggest chronic inflammatory changes in various tissues, due to exposure to toxic substances in tobacco snuff.…”

Theα4 Nicotinic Receptor Promotes CD4+T-Cell Proliferation and a Helper T-Cell Immune Response

“…4A). Because smoking has been shown to influence hematopoiesis (Pandit et al, 2006;Chang et al, 2010), the BMF was immunolabeled for a4, Gprin1, CD4, and the hematopoietic stem cell marker CD133 (Yin et al, 1997). As shown in Fig.…”