Radioprotective effects of flk2/flt3 ligand.
The radioprotective properties of flk2/flt3 ligand (FL) were evaluated in lethally irradiated mice. Optimum survival rates (70-80%) were observed when 5 to 20 microg of FL was administered at both 20 and 2 hours before LD100/30 radiation. Administration of FL well in advance of irradiation was essential for conferring most of the radioprotection, since a single dose given at -20 hours still resulted in a significant survival rate (65%), whereas a single dose given at -2 hours was relatively nonprotective. Histopathologic examination at 7 and 9 days postirradiation revealed significant myelopoietic activity in the bone marrow (BM) of FL-treated mice, suggesting that their survival might be due to sparing of radiosensitive hematopoietic cells. By comparison, the BM of mice treated with phosphate-buffered saline was extremely hypocellular and remained that way until they died of bacterial infection. Hematopoietic assays confirmed a marked stimulation of early white blood cell (WBC) recovery in the BM and blood of FL-protected mice relative to PBS-treated controls. By day 21, FL-protected mice showed circulating WBC numbers that were higher than preirradiation values; however, their BM colony-forming units in culture were still depressed. Moreover, these mice experienced a prolonged anemia and thrombocytopenia. These findings are discussed in light of the restricted subset of hematopoietic progenitors shown to be responsive to FL in vitro.
Hudak
S
S
Department of Immunobiology, DNAX Research Institute, Palo Alto, CA 94304, USA.
Leach
M W
MW
Xu
Y
Y
Menon
S
S
Rennick
D
D
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000528:radiation effects*; D007375:Interleukin-1 / Q000008:administration & dosage; D008565:Membrane Proteins / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D014916:Whole-Body Irradiation
D007375:Interleukin-1; D008565:Membrane Proteins; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; C084881:flt3 ligand protein