title: The differential role of human macrophage in triggering secondary bystander effects after either gamma-ray or carbon beam irradiation.
abstract: 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 γ-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 γ-irradiated NCI-H446 cells so that the secondary injuries in BEAS-2B cells under carbon ion irradiation were weaker than γ-rays. Both TNF-α and IL-1α were involved in the γ-irradiation induced secondary bystander effect but only TNF-α contributed to the carbon ion induced response. Further assay disclosed that IL-1α but not TNF-α 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.
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China; Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: He
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Tu
authors.affiliation: Research Development and Support Center, National Institute of Radiological Sciences, Inage, Chiba 263-8555, Japan.
authors.forename: Teruaki
authors.initials: T
authors.lastname: Konishi
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China; Central Laboratory, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, No. 509 Nanchang Road, Lanzhou 730000, China.
authors.forename: Bingrong
authors.initials: B
authors.lastname: Dang
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, No. 509 Nanchang Road, Lanzhou 730000, China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Li
authors.affiliation: Research Development and Support Center, National Institute of Radiological Sciences, Inage, Chiba 263-8555, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Uchihori
authors.affiliation: Department of Radiation Oncology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Tom K
authors.initials: TK
authors.lastname: Hei
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China. Electronic address: clshao@shmu.edu.cn.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D024201:Bystander Effect / Q000528:radiation effects*; D002250:Carbon Radioisotopes / Q000009:adverse effects; D018920:Coculture Techniques; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000009:adverse effects; D063193:Heavy Ion Radiotherapy / Q000009:adverse effects; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D018499:Linear Energy Transfer; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008262:Macrophage Activation / Q000528:radiation effects*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D048631:Micronucleus, Germline / Q000276:immunology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D015398:Signal Transduction / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020298:U937 Cells
chemical_list: D002250:Carbon Radioisotopes; C508584:IL1A protein, human; D053582:Interleukin-1alpha; D014409:Tumor Necrosis Factor-alpha
keywords: Cytokine signals; Irradiation; LET; Multi-cell lines; Secondary bystander effect