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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2243-2251.
Prepublished online as a Blood First Edition Paper on November 15, 2005; DOI 10.1182/blood-2005-02-0581.
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CHEMOKINES, CYTOKINES, AND INTERLEUKINS
Reduced retention of radioprotective hematopoietic cells within the bone marrow microenvironment in CXCR4–/– chimeric mice
Adlen Foudi,
Peggy Jarrier,
Yanyan Zhang,
Monika Wittner,
Jean-Francois Geay,
Yann Lecluse,
Takashi Nagasawa,
William Vainchenker, and
Fawzia Louache
From the National Institute for Health and Medical Research (INSERM) U362, IFR54, Institut Gustave Roussy, Villejuif, France; and Department of Medical Systems Control, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku Kyoto, Japan.
The physiologic role of CXCR4 on hematopoietic stem/progenitor cells (HSPCs) is not fully understood. Here, we show that radioprotection of lethally irradiated mice by embryonic day 14.5 (E14.5) CXCR4–/– fetal liver (FL) cells was markedly impaired when compared with CXCR4+/+ counterparts, but this defect was rescued when hosts were engrafted with high cell numbers. This quantitative defect contrasted with a similar content in hematopoietic colony-forming cells (CFCs), splenic colony-forming units (CFUs-S), and Lin– Sca-1+ c-kit+ cells in E14.5 CXCR4–/– and CXCR4+/+ livers. In addition, the homing of HSPCs in the bone marrow was not altered as detected with a CFSE-staining assay. In contrast, a 30-fold increase in CFCs was seen in the circulation of mice stably reconstituted with CXCR4–/– FL cells and this increment was already observed before hematopoiesis had reached a steady-state level. Together, the data strongly suggest that impaired retention may, at least in short-term hematopoietic reconstitution, lead to a diminution in the number of available progenitors required for radioprotection.
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