The cholinergic system is involved in regulation of the development of the hematopoietic system

Abstract

Gene expression profiling demonstrated that components of the cholinergic system, including choline acetyltransferase, acetylcholinesterase and nicotinic acetylcholine receptors (nAChRs), are expressed in embryonic stem cells and differentiating embryoid bodies (EBs). Triggering of nAChRs expressed in EBs by nicotine resulted in activation of MAPK and shifts of spontaneous differentiation toward hemangioblast. In vivo, non-neural nAChRs are detected early during development in fetal sites of hematopoiesis. Similarly, in vivo exposure of the developing embryo to nicotine resulted in higher numbers of hematopoietic progenitors in fetal liver. However postpartum, the number of hematopoietic stem/progenitor cells (HSPC) was decreased, suggesting an impaired colonization of the fetal bone marrow with HSPCs. This correlated with increased number of circulating HSPC and decreased expression of CXCR4 that mediates migration of circulating cells into the bone marrow regulatory niche. In addition, protein microarrays demonstrated that nicotine changed the profile of cytokines produced in the niche. While the levels of IL1α, IL1β, IL2, IL9 and IL10 were not changed, the production of hematopoiesis-supportive cytokines including G-CSF, GM-CSF, IL3, IL6 and IGFBP-3 was decreased. This correlated with the decreased repopulating ability of HSPC in vivo and diminished hematopoietic activity in bone marrow cultures treated with nicotine. Interestingly, nicotine stimulated the production of IL4 and IL5, implying a possible role of the cholinergic system in pathogenesis of allergic diseases. Our data provide evidence that the nicotine-induced imbalance of the cholinergic system during gestation interferes with normal development and provides the basis for negative health outcomes postpartum in active and passive smokers.

Human Platelets Express Functional α7-Nicotinic Acetylcholine Receptors

“…38 In an older report, cholinergic signaling during early megakaryopoiesis was described. 39 In our study, we found expression of the nAChR␣7 subunits in cells of the megakaryocytic lineage. This could be part of a functional cholinergic system involved in the regulation of megakaryopoiesis and thrombopoiesis.…”

Regulation of acetylcholine receptors during differentiation of bone mesenchymal stem cells harvested from human reaming debris

“…These parameters might also be responsible for the highly variable expression pattern of the individual donors. The presence of cholinergic receptors is confirmed in embryonic stem cells where mRNA of all nAChR α-and β-subunits [19] as well as all subtypes of mAChR was determined [9]. Functions of AChR on embryonic stem cells are (a) mobilization of intracellular Ca 2+ , and (b) an increase in viability without changes in proliferation [20].…”

Functional effects of antibodies against non-neuronal nicotinic acetylcholine receptors

“…This receptor has been found in many non-excitable cells and seems to play a universal signaling role due to its high permeability to Ca 2+ [3]. Previously we found that ␣7 nAChRs were present in the blood cells starting from the very early precursors [29]; they supported the lymphocyte survival in the course of differentiation, as well as propagation of mature lymphocytes in the spleens of mice treated with nicotine [12]. In contrast, either the absence of ␣7 nAChRs in ␣7 knockout mice [30] or their pharmacological blockade in the wild-type animals favored B lymphocyte activation in vitro and the antibody production in vivo [31].…”