The differential role of human macrophage in triggering secondary bystander effects after either gamma-ray or carbon beam irradiation

The abscopal effect could be an underlying factor in evaluating prognosis of radiotherapy. This study established an in vitro system to examine whether tumor-generated bystander signals could be transmitted by macrophages to further trigger secondary cellular responses after different irradiations, where human lung cancer NCI-H446 cells were irradiated with either gamma-rays or carbon ions and co-cultured with human macrophage U937 cells, then these U937 cells were used as a bystander signal transmitter and co-cultured with human bronchial epithelial cells BEAS-2B. Results showed that U937 cells were only activated by gamma-irradiated NCI-H446 cells so that the secondary injuries in BEAS-2B cells under carbon ion irradiation were weaker than gamma-rays. Both TNF-alpha and IL-1 alpha were involved in the gamma-irradiation induced secondary bystander effect but only TNF-alpha contributed to the carbon ion induced response. Further assay disclosed that IL-1 alpha but not TNF-alpha was largely responsible for the activation of macrophages and the formation of micronucleus in BEAS-2B cells. These data suggest that macrophages could transfer secondary bystander signals and play a key role in the secondary bystander effect of photon irradiation, while carbon ion irradiation has conspicuous advantage due to its reduced secondary injury. (C) 2015 Elsevier Ireland Ltd. All rights reserved.