Background: Radiation-induced pneumonitis and pulmonary fibrosis are common dose-limiting complications in patients receiving radiotherapy for lung, breast, and lymphoid cancers. In this study, we investigated the characteristics of effective immune cells related to pneumonitis and fibrosis after irradiation. Materials and Methods: After anesthesia, the whole thorax of C57BL/6 mice was irradiated at 14 Gy. The lung tissue and bronchoalveolar lavage fluid were collected at defined time points post-irradiation for the determination of histological and immunohistochemical analysis and inflammatory cell population infiltrated into the lung. Results and Discussion: Whole thoracic irradiation increased the deposition of extracellular matrix (ECM), lung weight, and pleural effusions, which started to die from 4 months later. At 4 months after irradiation, the numbers of macrophages and lymphocytes as well as neutrophils were increased dramatically in the lung. Interestingly, the macrophages that were recruited into the lung after irradiation had an enlarged foamy morphology. In addition, the expressions of chemokines (CCL-2, CCL-3, CXCL-10) for the attraction of macrophages and T cells were higher in the lung of irradiated mice. The high expressions of these chemokines were sustained up to 6 months following irradiation. In thoracic irradiated mice, infiltrated macrophages into the lung had the high levels of Mac-3 antigens on their surface and upregulated the hallmarks of alternatively activated macrophages such as arginase-1 and CD206. Furthermore, the levels of IL-4 and IL-13 were higher in a BAL fluid of irradiated mice. Conclusion: All results show that thoracic irradiation induces to infiltrate various inflammation- related immune cells, especially alternatively activated macrophages, through enhancing the expression of chemokines, suggesting that alternatively activated macrophages are most likely important for leading to pulmonary fibrosis.
목차
ABSTRACT Introduction Materials and Methods 1. Animals and Ethics Statement 2. Thoracic irradiation 3. Survivability and lung weight after irradiation 4. Determination of the volume of pleural exudates 5. Masson’s trichrome blue staining 6. cDNA microarray analysis 7. Preparation of total leukocytes from bronchoalvelolar lavage (BAL) fluid and differential counting 8. Preparation of total leukocytes from the lung tissue and flow cytometry analysis 9. Immunohistochemistry analysis 10. Analysis of the mRNA expression in the reverse transcriptase (RT)-polymerase chain reaction(PCR) 11. Western blotting 12. Measurement of cytokines in BAL fluid Results and Discussion 1. Thoracic irradiation-induced pneumonitis and pulmonary fibrosis 2. Thoracic irradiation induces the accumulation of extracellular matrix in the lung 3. Thoracic irradiation increases the recruitment of various immune cells into BAL fluid and the lung 4. Thoracic irradiation enhances the chemokines expression for the attraction of macrophages 5. Recruited macrophages after thoracic irradiation have Mac-3 antigen on their surface 6. Recruited macrophages after thoracic irradiation are alternatively activated macrophages, M2 macrophages Conclusion Acknowledgements References
Hae-Ran Park [ Radiation Division for Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Korea ]
Corresponding author
Sung-Kee Jo [ Radiation Division for Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Korea ]
Uhee Jung [ Radiation Division for Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Korea ]
대한방사선방어학회 [Korean Association For Radiation Protection]
설립연도
1975
분야
자연과학>기타자연과학
소개
회원 상호간의 협조와 친목을 도모함으로써 방사선방어에 관한 제반연구 및 발전에 이바지함을 물론 학술의 국제교류 및 국제학술단체와의 상호협력 증진에 기여함을 목적으로 하며, 이 목적을 달성하기 위하여 다음 각 호의 사업을 한다.
1. 방사선방어에 관한 학술연구발표회 및 강연회 등의 개최
2. 학회지 및 방사선방어에 관한 학술간행물의 발행 및 배포
3. 방사선방어에 관한 학술의 국제교류 및 협력
4. 방사선방어에 관한 국제학술자료의 조사, 수집 및 번역
5. 방사선방어에 관한 조사 및 연구용역
6. 회원의 연구활동을 위한 제반협조
7. 기타 본 학회의 목적 달성에 필요한 사항
간행물
간행물명
방사선방어학회지 [Journal of Radiation Protection and Research]