Abstract
Haemopoietic tissues exposed to ionizing radiation are shown to exhibit increased macrophage activation, defined by ultrastructural characteristics and increased lysosomal and nitric oxide synthase enzyme activities. Macrophage activation post-irradiation was also associated with enhanced respiratory burst activities and an unexpected neutrophil infiltration. Examination of p53-null mice demonstrated that macrophage activation and neutrophil infiltration were not direct effects of irradiation, but were a consequence of the recognition and clearance of radiation-induced apoptotic cells. Increased phagocytic cell activity was maintained after apoptotic bodies had been removed. These findings demonstrate that, contrary to expectation, recognition and clearance of apoptotic cells after exposure to radiation produces both a persistent macrophage activation and an inflammatory-type response. We also demonstrate a complexity of macrophage activation following radiation that is genotype dependent, indicating that the in vivo macrophage responses to radiation damage are genetically modified processes. These short-term responses of macrophages to radiation-induced apoptosis and their genetic modification are likely to be important determinants of the longer-term consequences of radiation exposure. Furthermore, in addition to any effects attributable to immediate radiation-induced damage, our findings provide a mechanism for the production of damage via a ‘bystander’ effect which may contribute to radiation-induced genomic instability and leukaemogenesis.
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The authors thank R Mitchell, S Macfarlane, J Gibbs, N Kernohan, M Boylan and R Pleass. The research was supported by grants from the Medical Research Council, the European Commission and the Leukaemia Research Fund.
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Lorimore, S., Coates, P., Scobie, G. et al. Inflammatory-type responses after exposure to ionizing radiation in vivo: a mechanism for radiation-induced bystander effects?. Oncogene 20, 7085–7095 (2001). https://doi.org/10.1038/sj.onc.1204903
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DOI: https://doi.org/10.1038/sj.onc.1204903
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