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

By Tamiko R. Katsumoto, Jennifer Duda, Andrew Kim, Zabihullah Wardak, Glenn Dranoff, D. Wade Clapp and Kevin Shannon

Abstract

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 β common subunit of the GM-CSF receptor (βc) 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 βc 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

Topics: Brief Definitive Report
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2213101
Provided by: PubMed Central
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