DELAYED NEUTROPHIL APOPTOSIS AFTER TOTAL-BODY IRRADIATION IN MICE - THE ROLE OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN NEUTROPHIL FUNCTION

We performed an in vitro study of the long-term effects of a sublethal dose (5 Gy) of x-irradiation on the survival and function of neutroph ils in adult mice. For this purpose, we incubated control neutrophils harvested from long-term bone marrow cultures (LTBMCs) with supernatan t withdrawn from cultures obtained in adult mice 6 or 9 months postirr adiation. We noted a significant increase in superoxide anion producti on, NADPH, and protein levels in these cells after 3, 6, and 15 hours of incubation compared with the same cells incubated with supernatant from control LTBMCs. We also observed a delay in apoptosis that was co rrelated with maintenance of adenosine triphosphate levels and surviva l. Similar differences were found when control LTBMC neutrophils were incubated with granulocyte-macrophage colony-stimulating factor (GM-CS F) (1.3 nM). Indeed, enzyme-linked immunosorbent assay revealed a sign ificant overproduction of this cytokine, together with higher interleu kin (IL)-6 and IL-3 levels, in the supernatant from cultures of irradi ated mice. Our results suggest that GM-CSF is one of the cytokines res ponsible for promoting the survival and activation of neutrophil funct ion after total body irradiation.