Nicotinic acetylcholine receptor-mediated stimulation of endothelial cells results in the arrest of haematopoietic progenitor cells on endothelium.

SummaryThe function of endothelial cells that contribute to the regulation ofhaematopoietic stem/progenitor cells (HSPC) migration from peripheralblood into bone marrow can be influenced by extrinsic factors includingnicotine. Therefore, the effect of nicotine on HSPC extravasation was studied.Using a parallel laminar flow chamber, we demonstrated an increase in thenumber of HSPC adhering to the nicotine-exposed endothelium underconditions of physiological shear stress in vitro. Nicotine-induced adhesion ofHSPC was inhibited by mecamylamine, a non-selective nicotinicacetylcholine receptor (nAchR) antagonist. The enhanced adhesiveinteractions of HSPC with nicotine-exposed endothelial monolayerscoincided with the nicotine-induced activation of endothelial cells.Nicotine induced fast cytoskeletal reorganization and formation offilopodia in endothelial cells through interaction with the non-neuronalnAchR expressed by these cells. In addition, nicotine treatment stimulatedrapid phosphorylation of Erk1/2 and p-38 in endothelial cells. Finally,nicotine inhibited the stroma derived factor-1-mediated transendothelialmigration of HSPC. Decreased migration of HSPC correlated withdiminished matrix metalloproteinase-9 activity secreted by bone marrowcells and decreased expression of CD44 on the surface of endothelial cells.Overall, our data suggest that exposure to nicotine causes endothelial celldysfunction and leads to the pathological arrest of HSPC on endothelium,interfering with their proper migration process.Keywords: stem cells, endothelial cells, cell surface molecules, cell trafficking,cell activation.