Synergy of IL-1 and stem cell factor in radioprotection of mice is associated with IL-1 up-regulation of mRNA and protein expression for c-kit on bone marrow cells

Journal Article · Mon Aug 15 04:00:00 EDT 1994 · Journal of Immunology

OSTI ID:86502

Neta, R ^[1]; Oppenheim, J J; Wang, J M ^[2]; Snapper, C M; Moorman, M A ^[3]; Dubois, C M ^[4]

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1. Armed Forces Radiobiology Research Institute, Bethesda, MD (United States)
2. National Cancer Institute, Frederick, MD (United States)
3. Uniformed Services Univ. for Health Sciences, Bethesda, MD (United States)
4. Univ. of Sherbrooke, Quebec (Canada)

Administration of IL-1 and stem cell factor (SCF) to mice 18 h before lethal {sup 60}Co whole-body irradiation resulted in synergistic radioprotection, as evidenced by increased numbers of mice surviving 1,200 to 1,300 cGy doses of radiation and the recovery of increased numbers of c-kit{sup +} bone marrow cells at 1 and 4 days after the lethal dose of 950 cGy. Anti-SCF Ab inhibited IL-1-induced radioprotection, indicating that endogenous production of SCF is necessary for radioprotection by IL-1. Conversely, radioprotection induced by SCF was reduced by anti-IL-1R Ab, indicating that endogenous IL-1 contributes to SCF radioprotection. SCF, unlike IL-1, does not induce hemopoietic CSFs and IL-6 or gene expression of a scavenging mitochondrial enzyme manganese superoxide dismutase in the bone marrow, suggesting that SCF and IL-1 radioprotect by distinct pathways. The mRNA expression for c-kit (by Northern blot analysis) and {sup 125}I-SCF binding on bone marrow cells was elevated within 2 and 4 h of IL-1 administration respectively. Four days after LD 100/30 radiation the recovery of c-kit{sup +} bone marrow cells was increased sixfold in IL-1-treated mice, almost 20-fold in SCF-treated mice, and 40-fold in mice treated with the combination of the two cytokines. Thus, endogenous production of both IL-1 and SCF is required for resistance to lethal irradiation and the synergistic radioprotective effect of the two cytokines may, in part, depend on IL-1 and SCF-induced increases in numbers of c-kit{sup +} hemopoietic stem and progenitors cells that survive lethal irradiation. 37 refs., 6 figs., 6 tabs.

• OSTI ID: 86502
• Journal Information: Journal of Immunology, Journal Name: Journal of Immunology Journal Issue: 4 Vol. 153; ISSN 0022-1767; ISSN JOIMA3
• Country of Publication: United States
• Language: English

Related Subjects

56 BIOLOGY AND MEDICINE
APPLIED STUDIES
GROWTH FACTORS
MESSENGER-RNA
MICE
RADIOSENSITIVITY
SYNERGISM
WHOLE-BODY IRRADIATION