Nicotinic acetylcholine receptors alpha4beta2 and alpha7 regulate myelo-and erythropoiesis within the bone marrow

Nicotine consumed upon smoking affects numerous physiological processes through nicotinic acetylcholine receptors, which mediate cholinergic regulation by the neuronal and endogenous acetylcholine. Consequently, nicotinic receptors are expressed in many non-excitable tissues including the blood. In spite of the documented effect of nicotine on hematopoiesis, little is known about the expression and role of nicotinic receptors in the course of blood cell differentiation. The aim of the present study was to investigate whether and how nicotinic receptors are involved in the development of myeloid and erythroid cells within the bone marrow. The presence of nicotinic receptors containing alpha 4(beta 2) and alpha 7 subunits in the bone marrow cells of C57B1/6 mice was shown by the binding of [I-125]-alpha-bungarotoxin or [H-3]-Epibatidine and by flow cytometry with subunit-specific antibodies or fluorescem-labeled alpha-cobratoxin. Both TER 119(+) (erythroid) and CD16(+)CD43(med) (myeloid) progenitor cells bound more alpha 4-specific antibodies than their mature forms, while the binding of alpha-cobratoxin and alpha 7-specific antibodies was also high in mature cells. According to morphological analysis, either the absence of alpha 7-containing nicotinic receptors in knockout mice or their desensitization in mice chronically treated with nicotine decreased the number of myeloid and erythroid progenitors and junior cells. In contrast, the absence of beta 2-containing receptors favored myelocyte generation and erythroid cell maturation. It is concluded that the development of both myeloid and erythroid cell lineages is regulated by endogenous cholinergoic ligands and can be affected by nicotine through alpha 7- and alpha 4 beta 2-containing nicotinic receptors, which play different roles in the course of the cell maturation. (C) 2007 Elsevier Ltd. All rights reserved.