A Potential Biomarker for Predicting the Risk of Radiation-Induced Fibrosis in the Lung
| Autor: | Bruce M. Fenton, Tanzy Love, Carl J. Johnston, Christina Reed, Jacob N. Finkelstein, Eric Hernady, Jacqueline P. Williams, Angela M. Groves |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Pulmonary Fibrosis Biophysics Lung injury Epithelial Damage 03 medical and health sciences Mice 0302 clinical medicine Biodosimetry Risk Factors Internal medicine medicine Animals Humans Uteroglobin Radiology Nuclear Medicine and imaging Mice Inbred C3H Radiation Lung business.industry Type-II Pneumocytes Surfactant protein D Pulmonary Surfactant-Associated Protein D Mice Inbred C57BL Radiation Pneumonitis 030104 developmental biology Club cell medicine.anatomical_structure 030220 oncology & carcinogenesis Potential biomarkers Female business Biomarkers |
| Zdroj: | Radiation research. 190(5) |
| ISSN: | 1938-5404 |
| Popis: | Biomarkers could play an essential role during triage in the aftermath of a radiological event, where exposure to radiation will be heterogeneous and complicated by concurrent trauma. Used alongside biodosimetry, biomarkers can identify victims in need of treatment for acute radiation effects, and might also provide valuable information on later developing consequences that need to be addressed as part of a treatment strategy. Indeed, because the lung is particularly sensitive to radiation and resultant late effects not only affect quality of life, but can also lead to morbidity, the risk of developing downstream pulmonary complications in exposed individuals requires assessment. In this study, analyses of changes in pulmonary and circulating content of club cell secretory protein (CCSP) and surfactant protein D (SP-D), expressed by epithelial club cells and type II pneumocytes in the lung, respectively, were used to evaluate pulmonary epithelial damage in several lung injury models. Using a combined radiation exposure model, fibrosis-susceptible C57BL/6J (C57) and alveolitis-prone C3H/HeJ (C3H) mice received 5 Gy total-body irradiation plus 2.5-10 Gy whole-lung irradiation, and lung and plasma samples were collected throughout the course of the radiation response, at time points ranging from 24 h to 26 weeks postirradiation. Radiation significantly reduced bronchiole CCSP coverage in C57 mice at 26 weeks, a response that varied in extent among animals, but correlated with the severity of fibrosis in each animal. Interestingly, plasma CCSP content was elevated in C57 mice at multiple time points preceding and during the fibrotic period; this response that was not observed in C3H mice. Circulating CCSP/SP-D ratios, calculated as an index of lung integrity, were similarly increased throughout the time course in C57, but not C3H, mice. Furthermore, when the thoracic doses were reduced to subthreshold levels for fibrosis induction (2.5 or 7.5 Gy), although the CCSP/SP-D ratio in lung homogenates demonstrated dose-responsive changes, this was not reflected in the plasma ratios at acute and late time points. Importantly, plasma CCSP/SP-D ratios also were not significantly altered in C57 mice exposed to LPS, and only transiently decreased in influenza-exposed mice, demonstrating a level of specificity for radiation-induced lung injury. These results indicate that the CCSP/SP-D ratio, measured in plasma, is sensitive to individual variation in radiation sensitivity, correlates with fibrosis development, can be detected early after exposure and is specific to radiation-induced injury. This suggests that the CCSP/SP-D ratio may be useful as a biomarker of radiation-induced pulmonary fibrosis. |
| Databáze: | OpenAIRE |
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