@article{3312eb6e125740e5b82a25865bd943e6,
title = "Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells",
abstract = "Steady-state egress of hematopoietic progenitor cells can be rapidly amplified by mobilizing agents such as AMD3100, the mechanism, however, is poorly understood. We report that AMD3100 increased the homeostatic release of the chemokine stromal cell derived factor-1 (SDF-1) to the circulation in mice and non-human primates. Neutralizing antibodies against CXCR4 or SDF-1 inhibited both steady state and AMD3100-induced SDF-1 release and reduced egress of murine progenitor cells over mature leukocytes. Intra-bone injection of biotinylated SDF-1 also enhanced release of this chemokine and murine progenitor cell mobilization. AMD3100 directly induced SDF-1 release from CXCR4 + human bone marrow osteoblasts and endothelial cells and activated uPA in a CXCR4/JNK-dependent manner. Additionally, ROS inhibition reduced AMD3100-induced SDF-1 release, activation of circulating uPA and mobilization of progenitor cells. Norepinephrine treatment, mimicking acute stress, rapidly increased SDF-1 release and progenitor cell mobilization, whereas β2-adrenergic antagonist inhibited both steady state and AMD3100-induced SDF-1 release and progenitor cell mobilization in mice. In conclusion, this study reveals that SDF-1 release from bone marrow stromal cells to the circulation emerges as a pivotal mechanism essential for steady-state egress and rapid mobilization of hematopoietic progenitor cells, but not mature leukocytes.",
keywords = "AMD3100, SDF-1/CXCR4, catecholamines, hematopoietic progenitor cells, rapid mobilization, uPA",
author = "Tsvee Lapidot and A. Dar and Amir Schajnovitz and Kfir Lapid and Alexander Kalinkovich and Tomer Itkin and Aya Ludin and W-M Kao and M. Battista and M. Tesio and Orit Kollet and Cohen, {N. N.} and Raanan Margalit and Buss, {E. C.} and F. Baleux and S. Oishi and N. Fujii and A. Larochelle and Dunbar, {C. E.} and Broxmeyer, {H. E.} and Frenette, {P. S.}",
note = "Helen and Martin Kimmel Institute for Stem Cell Research at the Weizmann Institute; Israeli Science Foundation [544/09]; European Union (Advance Cell-based Therapies for the Treatment of Primary Immunodeficiency) [HEALTH-F5-2010-261387]; Legacy Heritage Fund; National Institutes of Health; Ministry of Education, Culture, Sports, Science, and Technology of JapanThis study was partially supported by the Helen and Martin Kimmel Institute for Stem Cell Research at the Weizmann Institute, Israeli Science Foundation grant 544/09, the European Union (Advance Cell-based Therapies for the Treatment of Primary Immunodeficiency HEALTH-F5-2010-261387) and the Legacy Heritage Fund (TL). PSF is an established investigator of the American Heart Association supported by the National Institutes of Health. This work was also partially supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (SO and NF). TL holds The Edith Arnoff Stein Professorial Chair in Stem Cell Research. We would like to thank Dr Abraham Avigdor for supplying us with human BM aspirations from healthy donors and to Dr Scott Cooper for performing experiments with Anormed-derived AMD3100. Our special thanks to Drs Sara Rankin, Isabelle Petit, Shoham Shivtiel and Jonathan Canaani for fruitful discussions and for critically reviewing the manuscript.",
year = "2011",
month = aug,
doi = "https://doi.org/10.1038/leu.2011.62",
language = "الإنجليزيّة",
volume = "25",
pages = "1286--1296",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Springer Nature",
number = "8",
}
