Correlation between nicotine-induced inhibition of hematopoiesis and decreased CD44 expression on bone marrow stromal cells

This study demonstrates that in vivo exposure to cigarette smoke (CS) and i n vitro treatment of long-term bone marrow cultures (LTBMCs) with nicotine, a major constituent of CS, result in inhibition of hematopoiesis, Nicotine treatment significantly delayed the onset of hematopoietic foci and reduce d their size, Furthermore, the number of long-term culture-initiating cells (LTC-ICs) within an adherent layer of LTBMCs was significantly reduced in cultures treated with nicotine. Although the production of nonadherent matu re cells and their progenitors in nicotine treated LTBMCs was inhibited, th is treatment failed to influence the proliferation of Introduction committe d hematopoietic progenitors when added into methylcellulose cultures. Bone marrow stromal cells are an integral component of the hematopoietic microen vironment and play a critical role in the regulation of hematopoietic stem cell proliferation and self-renewal. Exposure to nicotine decreased CD44 su rface expression on primary bone marrow-derived fibroblastlike stromal cell s and MS-5 stromal cell line, but not on hematopoietic cells. In addition, mainstream CS altered the trafficking of hematopoietic stem/progenitor cell s (HSPC) in vivo. Exposure of mice to CS resulted in the inhibition of HSPC homing into bone marrow. Nicotine and cotinine treatment resulted in reduc tion of CD44 surface expression on lung microvascular endothelial cell line (LEISVO) and bone marrow-derived (STR-12) endothelial cell line. Nicotine treatment increased E-selectin expression on LEISVO cells, but not on STR-1 2 cells. These findings demonstrate that nicotine can modulate hematopoiesi s by affecting the functions of the hematopoiesis-supportive stromal microe nvironment, resulting in the inhibition of bone marrow seeding by LTC-ICs a nd interfering with stem cell homing by targeting microvascular endothelial cells. (C) 2001 by The American Society of Hematology.