The Journal of Experimental Medicine
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Published 21 March 2005. doi:10.1084/jem.20041504
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 6, 853-858
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BRIEF DEFINITIVE REPORT

 Granulocyte/macrophage colony-stimulating factor and accessory cells modulate radioprotection by purified hematopoietic cells

Tamiko R. Katsumoto1,2, Jennifer Duda1, Andrew Kim1, Zabihullah Wardak1, Glenn Dranoff3, D. Wade Clapp4, and Kevin Shannon1

1 Department of Pediatrics, University of California, San Francisco, CA 94143
2 Department of Internal Medicine, University of California, San Francisco, CA 94143
3 Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115
4 Department of Pediatrics and Herman B. Wells Center, Indiana University School of Medicine, Indianapolis, IN 46202

CORRESPONDENCE Kevin Shannon: kevins{at}itsa.ucsf.edu

Granulocyte/macrophage colony-stimulating factor (GM-CSF) promotes the survival, proliferation, and differentiation of myeloid lineage cells and regulates chemotaxis and adhesion. However, mice in which the genes encoding GM-CSF (Gmcsf) or the ß common subunit of the GM-CSF receptor (ßc) are inactivated display normal steady-state hematopoiesis. Here, we show that host GM-CSF signaling strongly modulates the ability of donor hematopoietic cells to radioprotect lethally irradiated mice. Although bone marrow mononuclear cells efficiently rescue Gmcsf mutant recipients, fetal liver cells and Sca1+ lin–/dim marrow cells are markedly impaired. This defect is partially attributable to accessory cells that are more prevalent in bone marrow. In contrast, Gmcsf-deficient hematopoietic stem cells demonstrate normal proliferative potentials. Short-term survival is also impaired in irradiated ßc mutant recipients transplanted with fetal liver or bone marrow. These data demonstrate a nonredundant function of GM-CSF in radioprotection by donor hematopoietic cells that may prove relevant in clinical transplantation.

J. Duda's present address is Stanford University Medical Center, Stanford, CA 94305.


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