Inhibition of c-kit ligand/steel factor by antibodies reduces survival of lethally irradiated mice.
Survival after irradiation with LD100/30 (radiation dose lethal to 100% of mice in 30 days) is based on recovery of impaired hematopoietic function. Our previous studies using antibodies to interleukin-1 receptor (IL-1R), tumor necrosis factor (TNF), and IL-6 demonstrated that endogenous production of these three cytokines is required for untreated mice as well as mice protected with lipopolysaccharide (LPS), IL-1, or TNF to survive lethal irradiation. In this report we show that anti-c-kit ligand/steel factor (SIF) antibody similarly abrogates LPS- and IL-1-induced radioprotection. Furthermore, administration of this antibody to unmanipulated mice increased LD50/30 radiation lethality from 50% to 100%. Such an effect was not obtained using anti-IL-3, anti-IL-4, or anti-granulocyte-macrophage colony-stimulating factor antibody. Thus, like IL-1, TNF, and IL-6, SIF is required for survival from lethal irradiation.
Neta
R
R
Department of Experimental Hematology, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889.
Williams
D
D
Selzer
F
F
Abrams
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D016298:Hematopoietic Cell Growth Factors / Q000276:immunology* / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017472:Receptors, Interleukin-1 / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D016298:Hematopoietic Cell Growth Factors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011837:Radiation-Protective Agents; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha