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Inhibition of c-kit ligand/steel factor by antibodies reduces survival of
lethally irradiated mice
R Neta, D Williams, F Selzer and J Abrams
Department of Experimental Hematology, Armed Forces Radiobiology Research
Institute, Bethesda, MD 20889.
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.
Volume 81,
Issue 2,
pp. 324-327,
01/15/1993
Copyright © 1993 by The American Society of Hematology
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