Granulocyte/macrophage colony-stimulating factor and accessory cells modulate radioprotection by purified hematopoietic cells.
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 beta common subunit of the GM-CSF receptor (betac) 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 betac 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.
Katsumoto
Tamiko R
TR
Department of Pediatrics, University of California, San Francisco, CA 94143, USA.
Duda
Jennifer
J
Kim
Andrew
A
Wardak
Zabihullah
Z
Dranoff
Glenn
G
Clapp
D Wade
DW
Shannon
Kevin
K
D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation / Q000528:radiation effects; D002469:Cell Separation; D005260:Female; D005333:Fetus / Q000166:cytology / Q000502:physiology; D005720:Gamma Rays; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000502:physiology; D051379:Mice; D023461:Myeloid Progenitor Cells / Q000502:physiology*; D038042:Myelopoiesis / Q000502:physiology / Q000528:radiation effects*; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects; D014916:Whole-Body Irradiation
D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor