1.Research progress on macrophage in radiation induced lung injury.
Mengyao LI ; Pan LIU ; Yuehai KE ; Xue ZHANG
Journal of Zhejiang University. Medical sciences 2020;49(5):623-628
Radiation-induced lung injury (RILI), including acute radiation pneumonitis and chronic radiation-induced pulmonary fibrosis (RIPF), is a side effect of radiotherapy for lung cancer and esophageal cancer. Pulmonary macrophages, as a kind of natural immune cells maintaining lung homeostasis, play a key role in the whole pathological process of RILI. In the early stage of RILI, classically activated M1 macrophages secrete proinflammatory cytokines to induce inflammation and produce massive reactive oxygen species (ROS) through ROS-induced cascade to further impair lung tissue. In the later stage of RILI, alternatively activated M2 macrophages secrete profibrotic cytokines to promote the development of RIPF. The roles of macrophage in the pathogenesis of RILI and the related potential clinical applications are summarized in this review.
Humans
;
Lung/radiation effects*
;
Lung Injury/physiopathology*
;
Macrophages/metabolism*
;
Radiation Injuries
;
Radiation Pneumonitis/etiology*
;
Radiotherapy/adverse effects*
2.Basic research of the relationship between irradiation dose and volume in radiation-induced pulmonary injury.
Qing-song PANG ; Ping WANG ; Jing WANG ; Wei WANG ; Jun WANG ; Zhi-yong YUAN
Chinese Medical Journal 2009;122(16):1929-1934
BACKGROUNDIrradiation dose and volume are the major physical factors of radiation-induced lung injury. The study investigated the relationships between the irradiation dose and volume in radiation-induced lung injury by setting up a model of graded volume irradiation of the rat lung.
METHODSAnimals were randomly assigned to three groups. The ELEKTA precise 2.03 treatment plan system was applied to calculate the irradiation dose and volume. The treatment plan for the three groups was: group 1 received a "high dose to a small volume" (25% volume group) with the mean irradiation volume being 1.748 cm(3) (25% lung volume); the total dose and mean lung dose (MLD) were 4610 cGy and 2006 cGy, respectively (bilateral AP-PA fields, source to axis distance (SAD) = 100 cm, 6MVX, single irradiation); Group 2 received a "low dose to a large volume" (100% volume group) with the mean irradiation volume being 6.99 cm(3) (100% lung volume); the total dose was 1153 cGy. MLD was 2006 cGy, which was the same as that of group 1 (bilateral AP-PA fields, SAD = 100 cm, 6MVX, single irradiation); Group 3 was a control group. With the exception of receiving no irradiation, group 3 had rest steps that were the same as those of the experimental groups. After irradiation, functional, histopathological, and CT changes were compared every two weeks till the 16th week.
RESULTSFunctionally, after irradiation breath rate (BR) increases were observed in both group 1 and group 2, especially during the period of 6th - 8th weeks. The changes of BR in the 100% volume group were earlier and faster. For the 25% volume group, although pathology was more severe, hardly any obvious increase in BR was observed. Radiographic changes were observed during the early period (the 4th week) and the most obvious changes manifested during the mediated period (the 8th week). The extensiveness of high density and the decreased lung permeability were presented in the 100% volume group, and ground glass opacity and patchy consolidation were presented in the 25% volume group without pleural effusion, pleural thickening, and lung shrinking. Morphologically, the 100% volume group mainly presented signs of vascular damage, including signs of vascular wall edemas, hypertrophy, and sclerosis. The 25% volume group mainly presented with erythrocyte cell exudation, inflammation, and parenchymal damage.
CONCLUSIONSThe delivery of a small dose of radiation to a large volume is not safe. A low dose smeared out over large volumes, albeit reversible, may lead to fatal respiratory dysfunction. Damage to the lung may be more dependent on the volume of irradiation than on the radiation dose. Clinically, the safest approach is to limit both the volume of the irradiated normal lung and the amount of received radiation.
Animals ; Dose-Response Relationship, Radiation ; Lung ; radiation effects ; Lung Injury ; etiology ; Radiation Injuries, Experimental ; Rats ; Rats, Wistar
3.Tumor necrosis factor-α enhances radiosensitivity of A549 cells.
Hui XIA ; Changhai YU ; Yiming ZHANG ; Jianqi YU ; Jie LI ; Wen ZHANG ; Yingjie LI
Journal of Southern Medical University 2012;32(4):565-568
OBJECTIVETo assess the effects of tumor necrosis factor-α (TNF-α) in enhancing the radiosensitivity of lung cancer cells in vitro.
METHODSA549 cells were exposed to γ-ray with or without TNF-α treatment. MTT assay was used to evaluate the cell viability, and flow cytometry was performed to assess the cell apoptosis. Western blotting was used to observe the expression of caspase-3 protein in the exposed cells.
RESULTSCompared with the exposed cells without TNF-α treatment, the cells treated with TNF-α showed significantly suppressed cell proliferation, increased the cell apoptosis, altered cell cycle, and increased caspase-3 protein expression after γ-ray exposure.
CONCLUSIONTNF-α can enhance the radiosensitivity of A549 cells to increase the efficiency of radiotherapy with γ-ray irradiation.
Apoptosis ; drug effects ; radiation effects ; Cell Cycle ; drug effects ; radiation effects ; Cell Line, Tumor ; Gamma Rays ; Humans ; Lung Neoplasms ; Radiation Tolerance ; drug effects ; Tumor Necrosis Factor-alpha ; pharmacology
4.Radiation Effect on NO, NOS and TGF-beta Expressions In Rat Lung.
Young Taek OH ; Kwang Joo PARK ; Hoon Jong KIL ; Mahn Joon HA ; Mison CHUN ; Seung Hee KANG ; Seong Eun PARK ; Sei Kyung CHANG
The Journal of the Korean Society for Therapeutic Radiology and Oncology 2000;18(4):321-328
PURPOSE: NOS2 induce NO production and NO activate TGF-beta. The TGF-beta is a inhibitor of NOS2. If this negative feedback mechanism operating in radiation pneumonitis model, NOS2 inhibitor may play a role in TGF-beta suppression. We planned this study to evaluate the expression patterns of NO, NOS2 and TGF-beta in vivo radiation pneumonitis model. MATERIALS AND METHODS: Sixty sprague-Dawley rat were irradiated 5 Gy or 20 Gy. They were sacrificed 3, 7, 14, 28 and 56 days after irradiation. During sacrifice, we performed broncho-alveolar lavage (BAL). The BAL fluids were centrifuged and supernatents were used for measure NO and TGF-beta, and the cells were used for RT-PCR. RESULTS: After 5 Gy of radiation, NO in BAL fluid increased at 28 days in both lung and TGF-beta in left lung at 56 days. NO increased in BAL fluid at 28 days in both lung after irradiation and TGF-beta in right lung at 28-56 days after 20 Gy of radiation. After 5 Gy of radiation, NOS2 expression was increased in right lung at 14 days, in both lung at 28 days and in left lung at 56 days. TGF-beta expression was reduced in both lung at 28 days and increased in left lung at 56 days. CONCLUSIONS: The proposed feedback mechanism of NO, NOS2 and TGF-beta was operated in vivo radiation pneumonitis model. At 56 days, however, NOS2 and TGF-beta expressed concurrently in left lung after 5 Gy and in both lung after 20 Gy of radiation.
Animals
;
Lung*
;
Radiation Effects*
;
Radiation Pneumonitis
;
Rats*
;
Rats, Sprague-Dawley
;
Therapeutic Irrigation
;
Transforming Growth Factor beta*
5.Abnormal shift of connexin 43 gap-junction protein induced by 50 Hz electromagnetic fields in Chinese hamster lung cells.
Qunli ZENG ; Genlin HU ; Huai CHIANG ; Yiti FU ; Guogen MAO ; Deqiang LU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2002;20(4):260-262
OBJECTIVETo study the effects of extremely low frequency magnetic fields(ELF MF) on the amount and localization of connexin 43(Cx43) gap-junction protein in the Chinese hamster lung(CHL) cells, and to explore the mechanism of ELF MF suppression on gap-junctional intercellular communication(GJIC).
METHODSThe cells were irradiated for 24 h with 50 Hz sinusoidal magnetic field at 0.8 mT without or with 12-O-tetrade-canoylphorbol-3-acetate(TPA), 5 ng/ml for 1 h. The localization of Cx43 proteins were performed by indirect immunofluorescence histochemical analysis and detected by confocal microscopy. The second experiment was conducted to examine the quantity of Cx43 proteins level in nuclei or cytoplasm and detected by Western blotting analysis.
RESULTSThe cells exposed to TPA for 1 h displayed less bright labelled spots in the regions of intercellular junction than the normal cells. Most of Cx43 labelled spots occurred in the cytoplasm and aggregated near the nuclei. At the same time, the amount of Cx43 protein in cytoplasm were increased[(2.03 +/- 0.89) in ELF group, (2.43 +/- 0.82) in TPA group] as compared to normal control(1.04 +/- 0.17) (P < 0.01).
CONCLUSIONInhibition on GJIC function by ELF MF alone or combined with TPA may be related with the shift of Cx43 from the regions of intercellular junction to the cytoplasm.
Animals ; Cell Communication ; radiation effects ; Connexin 43 ; biosynthesis ; Cricetinae ; Cricetulus ; Cytoplasm ; metabolism ; Electromagnetic Fields ; adverse effects ; Gap Junctions ; radiation effects ; Lung ; metabolism ; radiation effects ; Tetradecanoylphorbol Acetate ; pharmacology
6.Effects of power-frequency magnetic fields exposure on phosphorylation and enzymatic activity of stress-activated protein kinase and its upstream kinase.
Wenjun SUN ; Yingnian YU ; Yiti FU ; Huai CHIANG ; Haiyang XIE ; Deqiang LU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2002;20(4):256-259
OBJECTIVETo study the effects of 50 Hz power-frequency magnetic fields on signal transduction pathway of stress-activated protein kinase(SAPK), and explore the cellular signal transduction mechanism of the biological effects induced by power-frequency magnetic fields.
METHODSChinese hamster lung(CHL) cell line was exposed to power-frequency magnetic fields with two intensities for different exposure durations. The cytoplasmic protein was extracted and the phosphorylated portion of SAPK and SEK1/MKK4 was measured with Western blotting analysis. The SAPK enzymatic activity was measured by the solid-phase kinase assay in cells exposed to power-frequency magnetic fields for 15 min.
RESULTSBoth 0.4 mT and 0.8 mT power-frequency magnetic fields could enhance the phosphorylation of SAPK in a time-relative course manner, and reached the maximum extent at 15 min, with an increase of 20% and 17% respectively. The solid-phase kinase assay showed that the enzymatic activities of SAPK were also increased, which were 2.9 +/- 0.4 and 2.1 +/- 0.9 times of control respectively. However, the duration of SAPK phosphorylation induced by 0.8 mT was longer than that of 0.4 mT, while the duration and extent of SAPK dephosphorylation was remarkably shorter than that of 0.4 mT. The power-frequency magnetic fields under equal conditions could not phosphorylate(activate) the SEK1/MKK4.
CONCLUSIONPower-frequency magnetic fields could activate the SAPK, but not SEK1/MKK4. It is suggested that power-frequency magnetic fields may activate SAPK signal transduction pathway through a kinase other than SEK1/MKK4. The activation mechanism of SAPK of power-frequency magnetic fields needs to be identified in more detail.
Animals ; Cell Line ; Cricetinae ; Cricetulus ; Enzyme Activation ; radiation effects ; Lung ; metabolism ; radiation effects ; MAP Kinase Kinase 4 ; metabolism ; MAP Kinase Signaling System ; physiology ; radiation effects ; Magnetics ; Phosphorylation
7.Experimental study of effect of low power laser on telomere length of cells.
Ling HUANG ; Zhihui WU ; Hua MO
Journal of Biomedical Engineering 2013;30(3):592-596
To investigate the effect of low power helium neon laser (He-Ne laser) on the telomere length of human fetal lung diploid fibroblast (2BS) cell, we used the laser (gamma = 632. 8 nm, P = 2 mW) to treat the young 2BS cells. Cell growth and proliferation was observed through MTT method after treating with low power laser. The relative telomere length of 2BS cells was detected by fluorescence real-time quantitative PCR (q-PCR). The results showed that the cells of the treated groups grew better than the untreated groups. The telomere DNA length of the old 2BS cells, treated by low power He-Ne laser when they were young, was longer than that of untreated group. The results of the present study indicated that the low power He-Ne laser might decrease shortening rate of telomere and delay the aging of cells. Therefore, this study provides the experimental basis for us to further investigate the effect of low power laser on cell aging at the gene level.
Cell Line
;
Cellular Senescence
;
radiation effects
;
Fetus
;
Fibroblasts
;
cytology
;
Humans
;
Lasers
;
Lung
;
cytology
;
Telomere Homeostasis
;
radiation effects
8.Radiation Effect on Airway Obstruction from Lung Cancer.
Sei One SHIN ; Sung Kyu KIM ; Myung Se KIM
Yeungnam University Journal of Medicine 1989;6(2):121-125
Total 21 patients with airway obstruction from lung cancer treated with radiotherapy at Department of Therapeuctic Radiology, Yeungnam University College of Medicine, between April 1986 and December 1988 are retrospectively analyzed by means of roentgenologic findings. Obtained results are as follows. 1. 15 out of 21 patients (71%) showed complete or partial response. 2. Patients with small cell lung cancer showed 100% response in spite of low dose (30 GY/10 fractions.) 3. Patients with non-small cell lung cancer treated with 50 GY or over showed better response than below 45 GY or below. 4. There is no relationship between the response and site of airway obstruction. These date suggested that high dose irradiation is more effective in the management of airway obstruction from lung cancer and meticulous radiotherapy planning with appropriate protection of normal lung and critical organs should be investigated in order to maximize radiation effect and minimize side effect, complication or sequelae.
Airway Obstruction*
;
Carcinoma, Non-Small-Cell Lung
;
Humans
;
Lung Neoplasms*
;
Lung*
;
Radiation Effects*
;
Radiotherapy
;
Retrospective Studies
;
Small Cell Lung Carcinoma
9.Current situation and prospect of treatment for radiation-induced lung injury.
Xin LI ; Jianxin XUE ; You LU
Journal of Biomedical Engineering 2010;27(4):937-940
Radiation-induced lung injury (RILI) is the most common complication of the radiotherapy for thoracic tumor. It can lower the ratio of local control and seriously affect the patients' quality of life. At present, the clinical management of RILI is not more than the use of glucocorticoid and anti-inflammatory agent for symptomatic treatments. These treatments do not have any preventive effect but cause much side reactions. In this paper, we review the data from the contigency researches on the mechanism of RILI, from the researches on gene therapy and stem cell-therapy, and we dicuss the more safe, more stable and more efficacious treatment of RILI.
Antioxidants
;
therapeutic use
;
Genetic Therapy
;
methods
;
Humans
;
Lung
;
pathology
;
radiation effects
;
Lung Neoplasms
;
radiotherapy
;
Mesenchymal Stem Cell Transplantation
;
methods
;
Radiation Injuries
;
etiology
;
therapy
;
Radiation Pneumonitis
;
etiology
;
therapy
;
Radiation-Protective Agents
;
therapeutic use
;
Radiotherapy, Conformal
;
adverse effects
10.Suppression of low-dose hyper-radiosensitivity in human lung cancer cell line A549 by radiation-induced autophagy.
Yan-Xia ZHAO ; Chen CHENG ; Fang ZHU ; Hong-Ge WU ; Jing-Hua REN ; Wei-Hong CHEN ; Jing CHENG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2013;33(5):770-774
This study explored the role of radiation-induced autophagy in low-dose hyperradiosensitivity (HRS) in the human lung cancer cell line A549. A549 cells, either treated with an autophagic inhibitor 3-methyladenine (3-MA), or with a vehicle control, were irradiated at different low doses (≤0.5 Gy). The generation of autophagy was examined by laser scanning confocal microscopy. Western blotting was used to detect the expression of microtubule-associated protein l light chain 3B II (LC3B-II). Flow cytometry (FCM) and clonogenic assays were used to measure the fraction of surviving cells at the low irradiation doses. Our results showed that there was a greater inhibition of autophagic activity, but a higher degree of low-dose HRS in A549 cells treated with 3-MA than in control group. Our data demonstrated that radiation-induced autophagy is correlated with HRS in A549 cells, and is probably one of the mechanisms underlying HRS.
Adenine
;
analogs & derivatives
;
pharmacology
;
Autophagy
;
drug effects
;
radiation effects
;
Blotting, Western
;
Cell Line, Tumor
;
Cell Survival
;
drug effects
;
radiation effects
;
Dose-Response Relationship, Radiation
;
Flow Cytometry
;
Green Fluorescent Proteins
;
genetics
;
metabolism
;
Humans
;
Lung Neoplasms
;
genetics
;
metabolism
;
pathology
;
Microscopy, Confocal
;
Microscopy, Electron, Transmission
;
Microtubule-Associated Proteins
;
genetics
;
metabolism
;
Phagosomes
;
drug effects
;
radiation effects
;
ultrastructure
;
Radiation Tolerance
;
drug effects
;
radiation effects