Fibroblast Growth Factor-Peptide Promotes Bone Marrow Recovery After Irradiation
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Various members of the fibroblast growth factor (FGF) family mitigate radiation-induced damage. We designed and synthesized the binding domain peptide of FGF-2 (FGF-P) with a dimer form resistant to peptidase and examined its mitigatory effect on murine bone marrow cells. NIH Swiss mice were exposed to different doses of total body irradiation (TBI) and treated with ten doses of 5 mg/kg FGF-P. We achieved the following results: (1) FGF-P stimulated the growth of bone marrow cells harvested from mice exposed to 3 Gy; (2) on day 25 after 6 Gy TBI, the number of leukocytes and granulocytes was higher in the FGF-P group than in the vehicle-alone group; (3) FGF-P significantly increased the number of pro-B and pre-B cells; and (4) FGF-P treatment in vivo increased the long-term hematopoietic stem cells (LT-HSC) in bone marrow. These data reveal the underlying mechanism by which FGF-P rescued a significant percentage of the exposed mice. The increase of LT-HSC in bone marrow leads to a concomitant increase of pro-B and pre-B cells followed by leukocytes and granulocytes, which in turn enhance immunity against infection.
KeywordsBone marrow recovery Fibroblast growth factor-peptide Irradiation
This project is supported in part by U19 AI067733, RC1AI078519, RC2-AI-087580, RC1-AI081274 (NIAID/NIH), and Shands Cancer Center startup funds (University of Florida). We thank Dr. Chihray Liu and the medical physics faculty at UF for ensuring dosimetric accuracy in these experiments and Kate Casey-Sawicki for editing this manuscript.
- 2.TMT handbook. http://www.tmthandbook.org/. 18 Jul 2011