Inflammatory-type responses after exposure to ionizing radiation in vivo: a mechanism for radiation-induced bystander effects?

Haemopoietic tissues exposed to ionizing radiation are shown to exhibit inc reased macrophage activation, defined by ultrastructural characteristics an d increased lysosomal and nitric oxide synthase enzyme activities. Macropha ge activation post-irradiation was also associated with enhanced respirator y burst activities and an unexpected neutrophil infiltration. Examination o f p53-null mice demonstrated that macrophage activation and neutrophil infi ltration were not direct effects of irradiation, but were a consequence of the recognition and clearance of radiation-induced apoptotic cells. Increas ed phagocytic cell activity was maintained after apoptotic bodies had been removed. These findings demonstrate that, contrary to expectation, recognit ion and clearance of apoptotic cells after exposure to radiation produces b oth a persistent macrophage activation and an inflammatory-type response. W e also demonstrate a complexity of macrophage activation following radiatio n that is genotype dependent, indicating that the in vivo macrophage respon ses to radiation damage are genetically modified processes. These short-ter m responses of macrophages to radiation-induced apoptosis and their genetic modification are likely to be important determinants of the longer-term co nsequences of radiation exposure. Furthermore, in addition to any effects a ttributable to immediate radiation-induced damage, our findings provide a m echanism for the production of damage via a 'bystander' effect which may co ntribute to radiation-induced genomic instability and leukaemogenesis.