Modeling radiation-induced lung injury: lessons learned from whole thorax irradiation

References

• Abdollahi A, Li M, Ping G, Plathow C, Domhan S, Kiessling F, Lee LB, McMahon G, Grone HJ, Lipson KE. 2005. Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis. J Exp Med. 201:925–935.
   PubMed Web of Science ®Google Scholar
• Almeida C, Nagarajan D, Tian J, Leal SW, Wheeler K, Munley M, Blackstock W, Zhao W. 2013. The role of alveolar epithelium in radiation-induced lung injury. PLoS One. 8(1):e53628.
   PubMed Web of Science ®Google Scholar
• Ao X, Zhao L, Davis MA, Lubman DM, Lawrence TS, Kong FM. 2009. Radiation produces differential changes in cytokine profiles in radiation lung fibrosis sensitive and resistant mice. J Hematol Oncol. 2:6.
   PubMed Web of Science ®Google Scholar
• Aoshiba K, Tsuji T, Kameyama S, Itoh M, Semba S, Yamaguchi K, Nakamura H. 2013. Senescence-associated secretory phenotype in a mouse model of bleomycin-induced lung injury. Exp Toxicol Pathol. 65:1053–1062.
   PubMedGoogle Scholar
• Azzam EI, Jay-Gerin JP, Pain D. 2012. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Lett. 327:48–60.
   PubMed Web of Science ®Google Scholar
• Barnes JL, Gorin Y. 2011. Myofibroblast differentiation during fibrosis: role of NAD(P)H oxidases. Kidney Int. 79:944–956.
   PubMed Web of Science ®Google Scholar
• Baselet B, Belmans N, Coninx E, Lowe D, Janssen A, Michaux A, Tabury K, Raj K, Quintens R, Benotmane MA. 2017. Functional gene analysis reveals cell cycle changes and inflammation in endothelial cells irradiated with a single x-ray dose. Front Pharmacol. 8:213.
   PubMed Web of Science ®Google Scholar
• Beach TA, Johnston CJ, Groves AM, Williams JP, Finkelstein JN. 2017. Radiation induced pulmonary fibrosis as a model of progressive fibrosis: contributions of DNA damage, inflammatory response and cellular senescence genes. Exp Lung Res. 43:134–149.
   PubMed Web of Science ®Google Scholar
• Beach TA, Groves AM, Johnston CJ, Williams JP, Finkelstein JN. 2018. Recurrent DNA damage indicates persistent injury in progressive, radiation induced pulmonary fibrosis. Int J Radiat Biol. doi:10.1080/09553002.2018.1516907
   PubMed Web of Science ®Google Scholar
• Bickelhaupt S, Erbel C, Timke C, Wirkner U, Dadrich M, Flechsig P, Tietz A, Pfohler J, Gross W, Peschke P. 2017. Effects of ctgf blockade on attenuation and reversal of radiation-induced pulmonary fibrosis. J Natl Cancer Inst. 109. doi:10.1093/jnci/djw339
   PubMedGoogle Scholar
• Blackford AN, Jackson SP. 2017. Atm, atr, and DNA-pk: the trinity at the heart of the DNA damage response. Mol Cell. 66:801–817.
   PubMed Web of Science ®Google Scholar
• Bozyk PD, Moore BB. 2011. Prostaglandin e2 and the pathogenesis of pulmonary fibrosis. Am J Respir Cell Mol Biol. 45:445–452.
   PubMed Web of Science ®Google Scholar
• Campisi J. 2011. Cellular senescence: putting the paradoxes in perspective. Curr Opin Genet Dev. 21:107–112.
   PubMed Web of Science ®Google Scholar
• Campisi J, d'Adda di Fagagna F. 2007. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 8:729–740.
   PubMed Web of Science ®Google Scholar
• Chen C, Yang S, Zhang M, Zhang Z, Hong J, Han D, Ma J, Zhang SB, Okunieff P, Zhang L. 2016. Triptolide mitigates radiation-induced pulmonary fibrosis via inhibition of axis of alveolar macrophages-noxes-ros-myofibroblasts. Cancer Biol Ther. 17:381–389.
   PubMed Web of Science ®Google Scholar
• Cheresh P, Kim SJ, Tulasiram S, Kamp DW. 2013. Oxidative stress and pulmonary fibrosis. Biochim Biophys Acta. 1832:1028–1040.
   PubMed Web of Science ®Google Scholar
• Chiang CS, Liu WC, Jung SM, Chen FH, Wu CR, McBride WH, Lee CC, Hong JH. 2005. Compartmental responses after thoracic irradiation of mice: strain differences. Int J Radiat Oncol Biol Phys. 62:862–871.
   PubMed Web of Science ®Google Scholar
• Chilosi M, Carloni A, Rossi A, Poletti V. 2013. Premature lung aging and cellular senescence in the pathogenesis of idiopathic pulmonary fibrosis and copd/emphysema. Transl Res. 162:156–173.
   PubMed Web of Science ®Google Scholar
• Chung EJ, McKay-Corkum G, Chung S, White A, Scroggins BT, Mitchell JB, Mulligan-Kehoe MJ, Citrin D. 2016. Truncated plasminogen activator inhibitor-1 protein protects from pulmonary fibrosis mediated by irradiation in a murine model. Int J Radiat Oncol Biol Phys. 94:1163–1172.
   PubMed Web of Science ®Google Scholar
• Citrin DE, Prasanna PGS, Walker AJ, Freeman ML, Eke I, Barcellos-Hoff MH, Arankalayil MJ, Cohen EP, Wilkins RC, Ahmed MM, et al. 2017. Radiation-induced fibrosis: mechanisms and opportunities to mitigate. Report of an nci workshop, september 19, 2016. Radiat Res. 188:1–20.
   PubMed Web of Science ®Google Scholar
• Citrin DE, Shankavaram U, Horton JA, Shield W, 3rd, Zhao S, Asano H, White A, Sowers A, Thetford A, Chung EJ. 2013. Role of type ii pneumocyte senescence in radiation-induced lung fibrosis. J Natl Cancer Inst. 105:1474–1484.
   PubMedGoogle Scholar
• Coggle JE, Lambert BE, Moores SR. 1986. Radiation effects in the lung. Environ Health Perspect. 70:261–291.
   PubMed Web of Science ®Google Scholar
• Coppe JP, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J. 2008. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic ras and the p53 tumor suppressor. PLoS Biol. 6:2853–2868.
   PubMed Web of Science ®Google Scholar
• Dabjan MB, Buck CM, Jackson IL, Vujaskovic Z, Marples B, Down JD. 2016. A survey of changing trends in modelling radiation lung injury in mice: bringing out the good, the bad, and the uncertain. Lab Invest. 96:936–949.
   PubMed Web of Science ®Google Scholar
• Dadrich M, Nicolay NH, Flechsig P, Bickelhaupt S, Hoeltgen L, Roeder F, Hauser K, Tietz A, Jenne J, Lopez R, et al. 2016. Combined inhibition of TGFβ and PDGF signaling attenuates radiation-induced pulmonary fibrosis. Oncoimmunology. 5:e1123366.
   PubMed Web of Science ®Google Scholar
• de Leve S, Wirsdörfer F, Cappuccini F, Schütze A, Meyer AV, Röck K, Thompson LF, Fischer JW, Stuschke M, Jendrossek V. 2017. Loss of cd73 prevents accumulation of alternatively activated macrophages and the formation of prefibrotic macrophage clusters in irradiated lungs. Faseb J. 31:2869–2880.
   PubMed Web of Science ®Google Scholar
• Ding N-H, Li JJ, Sun L-Q. 2013. Molecular mechanisms and treatment of radiation-induced lung fibrosis. Curr Drug Targets. 14:1347–1346.
   PubMed Web of Science ®Google Scholar
• Down J, Steel G. 1983. The expression of early and late damage after thoracic irradiation: a comparison between cba and C57B1 mice. Radiat Res. 96:603.
   PubMed Web of Science ®Google Scholar
• Emami B, Lyman J, Brown A, Cola L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. 1991. Tolerance of normal tissue to therepeutic irradiation. Inr J Radiation Oncology Bio Phys. 21:109–122.
   PubMed Web of Science ®Google Scholar
• Epperly MW, Sikora CA, DeFilippi SJ, Gretton JE, Bar-Sagi D, Archer H, Carlos T, Guo H, Greenberger JS. 2002. Pulmonary irradiation-induced expression of VCAM-I and ICAM-I is decreased by manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) gene therapy. Biol Blood Marrow Transplant. 8:175–187.
   PubMed Web of Science ®Google Scholar
• Fajardo L, Berthronf M, Anderson R. 2001. Radiation pathology. New York: Oxford University Press.
   Google Scholar
• Farin AM, Manzo ND, Kirsch DG, Stripp BR. 2015. Low- and high-let radiation drives clonal expansion of lung progenitor cells in vivo. Radiat Res. 183:124–132.
   PubMed Web of Science ®Google Scholar
• Fleckenstein K, Zgonjanin L, Chen L, Rabbani Z, Jackson IL, Thrasher B, Kirkpatrick J, Foster WM, Vujaskovic Z. 2007. Temporal onset of hypoxia and oxidative stress after pulmonary irradiation. Int J Radiat Oncol Biol Phys. 68:196–204.
   PubMed Web of Science ®Google Scholar
• Flockerzi E, Schanz S, Rube CE. 2014. Even low doses of radiation lead to DNA damage accumulation in lung tissue according to the genetically-defined DNA repair capacity. Radiother Oncol. 111:212–218.
   PubMed Web of Science ®Google Scholar
• Freund A, Orjalo AV, Desprez PY, Campisi J. 2010. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med. 16:238–246.
   PubMed Web of Science ®Google Scholar
• Garofalo M, Bennett A, Farese AM, Harper J, Ward A, Taylor-Howell C, Cui W, Gibbs A, Lasio G, Jackson W. 3rd. 2014. The delayed pulmonary syndrome following acute high-dose irradiation: a rhesus macaque model. Health Phys. 106:56–72.
   PubMed Web of Science ®Google Scholar
• Gaugler C, Squiban A, VanDerMee MH. 1997. Late and persistent up-regulation of intercellular adhesion molecule-1 (icam-1) expression by ionizing radiation in human endothelial cells in vitro. Int J Radiat Biol. 72:201–209.
   PubMed Web of Science ®Google Scholar
• Ghosh SN, Wu Q, Mader M, Fish BL, Moulder JE, Jacobs ER, Medhora M, Molthen RC. 2009. Vascular injury after whole thoracic x-ray irradiation in the rat. Int J Radiat Oncol Biol Phys. 74:192–199.
   PubMed Web of Science ®Google Scholar
• Ginhoux F, Jung S. 2014. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol. 14:392–404.
   PubMed Web of Science ®Google Scholar
• Ginhoux F, Schultze JL, Murray PJ, Ochando J, Biswas SK. 2016. New insights into the multidimensional concept of macrophage ontogeny, activation and function. Nat Immunol. 17:34.
   PubMed Web of Science ®Google Scholar
• Graves PR, Siddiqui F, Anscher MS, Movsas B. 2010. Radiation pulmonary toxicity: from mechanisms to management. Semin Radiat Oncol. 20:201–207.
   PubMed Web of Science ®Google Scholar
• Groover T, Christie AC., Merritt E. 1923. Interthoracic changes following roentgen treatment of breast carcinoma. Am Journal of Roetgenology. 10(10):471–476.
   Google Scholar
• Gross N. 1981. The pathogenesis of radiation-induced lung damage. Lung. 159:115–125.
   PubMed Web of Science ®Google Scholar
• Gross N, Balis J. 1978. Functional, biochemical, and morphologic changes in alveolar macrophages following thoracic x-irradiation. Lab Invest. 39:381–389.
   PubMed Web of Science ®Google Scholar
• Groves AM, Johnston CJ, Misra RS, Williams JP, Finkelstein JN. 2015. Whole-lung irradiation results in pulmonary macrophage alterations that are subpopulation and strain specific. Radiat Res. 184:639–649.
   PubMed Web of Science ®Google Scholar
• Groves AM, Johnston CJ, Misra RS, Williams JP, Finkelstein JN. 2016. Effects of il-4 on pulmonary fibrosis and the accumulation and phenotype of macrophage subpopulations following thoracic irradiation. Int J Radiat Biol. 92:754–765.
   PubMed Web of Science ®Google Scholar
• Groves AM, Johnston CJ, Williams JP, Finkelstein JN. 2018. Role of infiltrating monocytes in the development of radiation-induced pulmonary fibrosis. Radiat Res. 189:300–311.
   PubMed Web of Science ®Google Scholar
• Gudkov AV, Komarova EA. 2003. The role of p53 in determining sensitivity to radiotherapy. Nat Rev Cancer. 3:117–129.
   PubMed Web of Science ®Google Scholar
• Hall E, Giaccia A. 2012. Radiobiology for the radiobiologist.7th ed. Philadelphia: Lippincott Williams and Wilkins.
   Google Scholar
• Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB, Leboeuf M, Becker CD, See P, Price J, Lucas D, et al. 2013. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. 38:792–804.
   PubMed Web of Science ®Google Scholar
• Helton ES, Chen X. 2007. P53 modulation of the DNA damage response. J Cell Biochem. 100:883–896.
   PubMed Web of Science ®Google Scholar
• Hernando M, Marks L, Bentel G, Zhou S, Hollis D, Das S, Fan M, Munley M, Shafman T, Anscher M, et al. 2001. Radiation induced pulmonary toxicity: a dose-volume histogram analysis. Int J Radiation Oncology Biol Phys. 51:650–659.
   PubMed Web of Science ®Google Scholar
• Hogan BL, Barkauskas CE, Chapman HA, Epstein JA, Jain R, Hsia CC, Niklason L, Calle E, Le A, Randell SH, et al. 2014. Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function. Cell Stem Cell. 15:123–138.
   PubMed Web of Science ®Google Scholar
• Hong J-H, Jung S-M, Tsao TCY, Wu C-J, Lee C-Y, Chen F-H, Hsu C-H, Mcbride WH, Chiang C-S. 2003. Bronchoalveolar lavage and interstitial cells have different roles in radiation-induced lung injury. Int J Radiat Biol. 79:159–167.
   PubMed Web of Science ®Google Scholar
• Hopewell W, Rezvani M, Moustafa H. 2000. The pig as a model for the study of radiation effects on the lung. Int J Radiat Biol. 76:447–452.
   PubMed Web of Science ®Google Scholar
• Hunninghake GW, Kawanami O, Ferrans VJ, Young Jr RC, Roberts WC, Crystal RG. 1981. Characterization of the inflammatory and immune effector cells in the lung parenchyma of patients with interstitial lung disease. Am Rev Respir Dis. 123(4):407–412.
   PubMedGoogle Scholar
• Igarashi K, Sakimoto I, Kataoka K, Ohta K, Miura M. 2007. Radiation-induced senescence-like phenotype in proliferating and plateau-phase vascular endothelial cells. Exp Cell Res. 313:3326–3336.
   PubMed Web of Science ®Google Scholar
• Iwabuchi K, Li B, Massa HF, Trask BJ, Date T, Fields S. 1998. Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53bp1 and 53bp2. J Biol Chem. 273:26061–26068.
   PubMed Web of Science ®Google Scholar
• Jackson IL, Vujaskovic Z, Down J. 2011. A further comparison of pathologies after thoracic irradiation among different mouse strains: finding the best preclinical model for evaluating therapies directed against radiation-induced lung damage. Radiat Res. 175:510–518.
   PubMed Web of Science ®Google Scholar
• Jackson IL, Xu PT, Nguyen G, Down JD, Johnson CS, Katz BP, Hadley CC, Vujaskovic Z. 2014. Characterization of the dose response relationship for lung injury following acute radiation exposure in three well-established murine strains: developing an interspecies bridge to link animal models with human lung. Health Phys. 106:48–55.
   PubMed Web of Science ®Google Scholar
• Johnston CJ, Hernady E, Reed C, Thurston SW, Finkelstein JN, Williams JP. 2010. Early alterations in cytokine expression in adult compared to developing lung in mice after radiation exposure. Radiat Res. 173:522–535.
   PubMed Web of Science ®Google Scholar
• Johnston CJ, Williams JP, Okunieff P, Finkelstein J. 2002. Radiation-induced pulmonary fibrosis: examination of chemokine and chemokine receptor families. Radiat Res. 157:256–265.
   PubMed Web of Science ®Google Scholar
• Johnston CJ, Wright T, Rubin P, Finkelstein JN. 1998. Alterations in the expression of chemokine mrna levels in fibrosis-resistant and -sensitive mice after thoracic irradiation. Exp Lung Res. 24:321–337.
   PubMed Web of Science ®Google Scholar
• Johnston CJ, Piedboeuf B, Rubin P, Williams JP, Baggs R, Finkelstein JN. 1996. Early and persistent alterations in the expression of interleukin-1a, interleukin-1b and tumor necrosis factor a mrna levels in fibrosis-resistant and sensitive mice after thoracic irradiation. Radiat Res. 145:762–767.
   PubMed Web of Science ®Google Scholar
• Kalash R, Berhane H, Au J, Rhieu BH, Epperly MW, Goff J, Dixon T, Wang H, Zhang X, Franicola D, et al. 2014. Differences in irradiated lung gene transcription between fibrosis-prone c57bl/6nhsd and fibrosis-resistant c3h/henhsd mice. In Vivo. 28:147–171.
   PubMed Web of Science ®Google Scholar
• Kalash R, Berhane H, Goff J, Houghton F, Epperly MW, Dixon T, Zhang X, Sprachman MM, Wipf P, Franicola D, et al. 2013. Effects of thoracic irradiation on pulmonary endothelial compared to alveolar type-ii cells in fibrosis-prone c57bl/6ntac mice. In Vivo. 27:291–297.
   PubMed Web of Science ®Google Scholar
• Kang SK, Rabbani ZN, Folz RJ, Golson ML, Huang H, Yu D, Samulski TS, Dewhirst MW, Anscher MS, Vujaskovic Z. 2003. Overexpression of extracellular superoxide dismutase protects mice from radiation-induced lung injury. Int J Radiat Oncol Biol Phys. 57:1056–1066.
   PubMed Web of Science ®Google Scholar
• Kharofa J, Cohen EP, Tomic R, Xiang Q, Gore E. 2012. Decreased risk of radiation pneumonitis with incidental concurrent use of angiotensin-converting enzyme inhibitors and thoracic radiation therapy. Int J Radiat Oncol Biol Phys. 84:238–243.
   PubMed Web of Science ®Google Scholar
• Kim GJ, Chandrasekaran K, Morgan WF. 2006. Mitochondrial dysfunction, persistently elevated levels of reactive oxygen species and radiation-induced genomic instability: a review. Mutagenesis. 21:361–367.
   PubMed Web of Science ®Google Scholar
• Kim GJ, Fiskum GM, Morgan WF. 2006. A role for mitochondrial dysfunction in perpetuating radiation-induced genomic instability. Cancer Res. 66:10377–10383.
   PubMed Web of Science ®Google Scholar
• Kliment CR, Oury TD. 2010. Oxidative stress, extracellular matrix targets, and idiopathic pulmonary fibrosis. Free Radic Biol Med. 49:707–717.
   PubMed Web of Science ®Google Scholar
• Kma L, Gao F, Fish BL, Moulder JE, Jacobs ER, Medhora M. 2012. Angiotensin converting enzyme inhibitors mitigate collagen synthesis induced by a single dose of radiation to the whole thorax. J Radiat Res. 53:10–17.
   PubMed Web of Science ®Google Scholar
• Kropski JA, Fremont RD, Calfee CS, Ware LB. 2009. Clara cell protein (cc16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury. Chest. 135:1440–1447.
   PubMed Web of Science ®Google Scholar
• Kunwar A, Haston CK. 2015. DNA damage at respiratory distress, but not acute time-points, correlates with tissue fibrosis following thoracic radiation exposure in mice. Int J Radiat Biol. 91:360–367.
   PubMed Web of Science ®Google Scholar
• Leach KJ, Tuyle GV, Lin P.S., Schmidt-Ullrich R, Mikkelsen R. 2001. Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen-nitrogen. Cancer Res. 61:3894–3901.
   PubMed Web of Science ®Google Scholar
• Lebrun A, Lo Re S, Chantry M, Izquierdo Carerra X, Uwambayinema F, Ricci D, Devosse R, Ibouraadaten S, Brombin L, Palmai-Pallag M, et al. 2017. Ccr2+ monocytic myeloid-derived suppressor cells (M-MDSCs) inhibit collagen degradation and promote lung fibrosis by producing transforming growth factor-β1. J Pathol. 243:320–330.,
   PubMed Web of Science ®Google Scholar
• Lee J-G, Park S, Bae C-H, Jang W-S, Lee S-J, Lee DN, Myung JK, Kim CH, Jin Y-W, Lee S-S, et al. 2016. Development of a minipig model for lung injury induced by a single high-dose radiation exposure and evaluation with thoracic computed tomography. J Radiat Res. 57:201–209.
   PubMed Web of Science ®Google Scholar
• Liu G, Cheresh P, Kamp DW. 2013. Molecular basis of asbestos-induced lung disease. Annu Rev Pathol. 8:161–187.
   PubMed Web of Science ®Google Scholar
• Liu RM, Gaston Pravia KA. 2010. Oxidative stress and glutathione in tgf-beta-mediated fibrogenesis. Free Radic Biol Med. 48:1–15.
   PubMed Web of Science ®Google Scholar
• Lu T, Finkel T. 2008. Free radicals and senescence. Exp Cell Res. 314:1918–1922.
   PubMed Web of Science ®Google Scholar
• Machtay M, Scherpereel A, Santiago J, Lee J, McDonough J, Kinniry P, Arguiri E, Shuvaev VV, Sun J, Cengel K, et al. 2006. Systemic polyethylene glycol-modified (pegylated) superoxide dismutase and catalase mixture attenuates radiation pulmonary fibrosis in the c57bl6 mouse. Radiother Oncol. 81:196–205.
   PubMed Web of Science ®Google Scholar
• MacVittie TJ, Gibbs A, Farese AM, Barrow K, Bennett A, Taylor-Howell C, Kazi A, Prado K, Parker G, Jackson W. III. 2017. Aeol 10150 mitigates radiation-induced lung injury in the nonhuman primate: morbidity and mortality are administration schedule-dependent. Radiat Res. 187:298–318.
   PubMed Web of Science ®Google Scholar
• Mahmood J, Jelveh S, Zaidi A, Doctrow SR, Hill RP. 2013. Mitigation of radiation-induced lung injury with euk-207 and genistein: effects in adolescent rats. Radiat Res. 179:125–134.
   PubMed Web of Science ®Google Scholar
• Mahmood J, Jelveh S, Zaidi A, Doctrow SR, Medhora M, Hill RP. 2014. Targeting the renin-angiotensin system combined with an antioxidant is highly effective in mitigating radiation-induced lung damage. Int J Radiat Oncol Biol Phys. 89:722–728.
   PubMed Web of Science ®Google Scholar
• Maier P, Hartmann L, Wenz F, Herskind C. 2016. Cellular pathways in response to ionizing radiation and their targetability for tumor radiosensitization. Int J Mol Sci. 17(1). doi:10.3390/ijms17010102
   PubMed Web of Science ®Google Scholar
• Malaviya R, Gow AJ, Francis M, Abramova EV, Laskin JD, Laskin DL. 2015. Radiation-induced lung injury and inflammation in mice: role of inducible nitric oxide synthase and surfactant protein d. Toxicol Sci. 144:27–38.
   PubMed Web of Science ®Google Scholar
• Manning CM, Johnston CJ, Hernady E, Miller JN, Reed CK, Lawrence BP, Williams JP, Finkelstein JN. 2013. Exacerbation of lung radiation injury by viral infection: the role of clara cells and clara cell secretory protein. Radiat Res. 179:617–629.
   PubMed Web of Science ®Google Scholar
• Martin M, Lefaix J, Delanian S. 2000. TGF-beta1 and radiation fibrosis: a master switch and a specific therapeutic target?. Int J Radiat Oncol Biol Phys. 47:277–290.
   PubMed Web of Science ®Google Scholar
• McBride WH, Chiang C-S, Olson JL, Wang C-C, Hong J-H, Pajonk F, Dougherty GJ, Iwamoto KS, Pervan M, Liao Y-P. 2004. A sense of danger from radiation. Radiat Res. 162:1–19.
   PubMed Web of Science ®Google Scholar
• McDonald S, Rubin P, Constine L, Williams JP, Finkelstein J, Smudzin T. 1995. Biochemical markers as predictors for pulmononary effects of radiation. Radiat Oncol Investig. 3:56–63.
   Google Scholar
• McDonald S, Rubin P, Phillips T, Marks L. 1995. Injury to the lung from cancer therapy- clinical syndromes, potential endpoints and scoring systems. Int J Radiation Oncology Biol Phys. 31:1187–1203.
   PubMed Web of Science ®Google Scholar
• Meziani L, Mondini M, Petit B, Boissonnas A, de Montpreville VT, Mercier O, Vozenin M-C, Deutsch E. 2018. Csf1r inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages. Eur Respir J. 51:1702120.
   PubMed Web of Science ®Google Scholar
• Minagawa S, Araya J, Numata T, Nojiri S, Hara H, Yumino Y, Kawaishi M, Odaka M, Morikawa T, Nishimura SL, et al. 2011. Accelerated epithelial cell senescence in ipf and the inhibitory role of sirt6 in TGF-β-induced senescence of human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 300:L391–L401.
   PubMed Web of Science ®Google Scholar
• Misharin AV, Morales-Nebreda L, Reyfman PA, Cuda CM, Walter JM, McQuattie-Pimentel AC, Chen C-I, Anekalla KR, Joshi N, Williams KJN, et al. 2017. Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span. J Exp Med. 214:2387–2404.
   PubMed Web of Science ®Google Scholar
• Morgan W, Sowa M. 2015. Non-targeted effects induced by ionizing radiation: mechanisms and potential impact on radiation induced health effects. Cancer Lett. 356:17–21.
   PubMed Web of Science ®Google Scholar
• Morgan GW, Pharm B, Breit SN. 1995. Radiation and the lung: a reevaluation of the mechanisms mediating pulmonary injury. Int J Radiat Oncol Biol Phys. 31:361–369.
   PubMed Web of Science ®Google Scholar
• Morikawa M, Derynck R, Miyazono K. 2016. Tgf-beta and the tgf-beta family: context-dependent roles in cell and tissue physiology. Cold Spring Harb Perspect Biol. 8:a021873.
   PubMed Web of Science ®Google Scholar
• Moses HL, Roberts AB, Derynck R. 2016. The discovery and early days of tgf-beta: a historical perspective. Cold Spring Harb Perspect Biol. 8(7). doi:10.1101/cshperspect.a021865
   PubMed Web of Science ®Google Scholar
• Mühlfeld C, Madsen J, Mackay R-M, Schneider JP, Schipke J, Lutz D, Birkelbach B, Knudsen L, Botto M, Ochs M, et al. 2017. Effect of irradiation/bone marrow transplantation on alveolar epithelial type ii cells is aggravated in surfactant protein d deficient mice. Histochem Cell Biol. 147:49–61.
   PubMed Web of Science ®Google Scholar
• Munoz-Espin D, Serrano M. 2014. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol. 15:482–496.
   PubMed Web of Science ®Google Scholar
• Murigi FN, Mohindra P, Hung C, Salimi S, Goetz W, Pavlovic R, Jackson IL, Vujaskovic Z. 2015. Dose optimization study of aeol 10150 as a mitigator of radiation-induced lung injury in cba/j mice. Radiat Res. 184:422–432.
   PubMed Web of Science ®Google Scholar
• Murray LA, Chen Q, Kramer MS, Hesson DP, Argentieri RL, Peng X, Gulati M, Homer RJ, Russell T, van Rooijen N, et al. 2011. Tgf-beta driven lung fibrosis is macrophage dependent and blocked by serum amyloid p. Int J Biochem Cell Biol. 43:154–162.
   PubMed Web of Science ®Google Scholar
• Oh CW, Bump EA, Kim J-S, Janigro D, Mayberg MR. 2001. Induction of a senescence-like phenotype in bovine aortic endothelial cells by ionizing radiation. Radiat Res. 156:232–240.
   PubMed Web of Science ®Google Scholar
• Olive PL. 1998. The role of DNA single- and double-strand breaks in cell killing by ionizing radiation. Radiat Res. 150:S42–S51.
   PubMed Web of Science ®Google Scholar
• Ortega-Gómez A, Perretti M, Soehnlein O. 2013. Resolution of inflammation: an integrated view. EMBO Mol Med. 5:661–674.
   PubMed Web of Science ®Google Scholar
• Osterholzer JJ, Olszewski MA, Murdock BJ, Chen G-H, Erb-Downward JR, Subbotina N, Browning K, Lin Y, Morey RE, Dayrit JK, et al. 2013. Implicating exudate macrophages and ly-6chigh monocytes in ccr2-dependent lung fibrosis following gene-targeted alveolar injury. J Immunol. 190:3447–3457.
   PubMed Web of Science ®Google Scholar
• Pan J, Li D, Xu Y, Zhang J, Wang Y, Chen M, Lin S, Huang L, Chung EJ, Citrin DE, et al. 2017. Inhibition of bcl-2/xl with abt-263 selectively kills senescent type ii pneumocytes and reverses persistent pulmonary fibrosis induced by ionizing radiation in mice. Int J Radiat Oncol Biol Phys. 99:353–361.
   PubMed Web of Science ®Google Scholar
• Panganiban RA, Day RM. 2013. Inhibition of igf-1r prevents ionizing radiation-induced primary endothelial cell senescence. PLoS One. 8:e78589.
   PubMed Web of Science ®Google Scholar
• Panganiban RA, Mungunsukh O, Day RM. 2013. X-irradiation induces er stress, apoptosis, and senescence in pulmonary artery endothelial cells. Int J Radiat Biol. 89:656–667.
   PubMed Web of Science ®Google Scholar
• Paun A, Kunwar A, Haston CK. 2015. Acute adaptive immune response correlates with late radiation-induced pulmonary fibrosis in mice. Radiat Oncol. 10:45.
   PubMed Web of Science ®Google Scholar
• Peel D, Coggle J. 1980. The effect of x irradiation on alveolar macrophages in mice. Radiat Res. 81:10–19.
   PubMed Web of Science ®Google Scholar
• Perl A-KT, Riethmacher D, Whitsett JA. 2011. Conditional depletion of airway progenitor cells induces peribronchiolar fibrosis. Am J Respir Crit Care Med. 183:511–521.
   PubMed Web of Science ®Google Scholar
• Rangarajan S, Locy ML, Luckhardt TR, Thannickal VJ. 2016. Targeted therapy for idiopathic pulmonary fibrosis: where to now?. Drugs. 76:291–300.
   PubMed Web of Science ®Google Scholar
• Richardson RB. 2009. Ionizing radiation and aging: rejuvenating an old idea. Aging (Albany NY). 1:887–902.
   PubMedGoogle Scholar
• Robbins ME, Diz DI. 2006. Pathogenic role of the renin-angiotensin system in modulating radiation-induced late effects. Int J Radiat Oncol Biol Phys. 64:6–12.
   PubMed Web of Science ®Google Scholar
• Robbins ME, Zhao W. 2004. Chronic oxidative stress and radiation-induced late normal tissue injury: a review. Int J Radiat Biol. 80:251–259.
   PubMed Web of Science ®Google Scholar
• Rodemann HP, Blaese MA. 2007. Responses of normal cells to ionizing radiation. Semin Radiat Oncol. 17:81–88.
   PubMed Web of Science ®Google Scholar
• Rodier F, Coppe JP, Patil CK, Hoeijmakers WA, Munoz DP, Raza SR, Freund A, Campeau E, Davalos AR, Campisi J. 2009. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol. 11:973–979.
   PubMed Web of Science ®Google Scholar
• Rodier F, Munoz DP, Teachenor R, Chu V, Le O, Bhaumik D, Coppe J-P, Campeau E, Beausejour CM, Kim S-H, et al. 2011. DNA-scars: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion. J Cell Sci. 124:68–81.
   PubMed Web of Science ®Google Scholar
• Romero F, Shah D, Duong M, Penn RB, Fessler MB, Madenspacher J, Stafstrom W, Kavuru M, Lu B, Kallen CB, et al. 2015. A pneumocyte-macrophage paracrine lipid axis drives the lung toward fibrosis. Am J Respir Cell Mol Biol. 53:74–86.
   PubMed Web of Science ®Google Scholar
• Rothkamm K, Barnard S, Moquet J, Ellender M, Rana Z, Burdak-Rothkamm S. 2015. DNA damage foci: meaning and significance. Environ Mol Mutagen. 56:491–504.
   PubMed Web of Science ®Google Scholar
• Rübe CE, Uthe D, Schmid KW, Richter KD, Wessel J, Schuck A, Willich N, Rübe C. 2000. Dose-dependent induction of transforming growth factor β (tgf-β) in the lung tissue of fibrosis-prone mice after thoracic irradiation. Int J Radiat Oncol Biol Phys. 47:1033–1042.
   PubMed Web of Science ®Google Scholar
• Rübe CE, Uthe D, Wilfert F, Ludwig D, Yang K, König J, Palm J, Schuck A, Willich N, Remberger K, et al. 2005. The bronchiolar epithelium as a prominent source of pro-inflammatory cytokines after lung irradiation. Int J Radiat Oncol Biol Phys. 61:1482–1492.
   PubMed Web of Science ®Google Scholar
• Rubin P, Casarett G. 1968. Clinical radiation pathology. Vol. 1 and 2. Philadelphia, PS: Saunders.
   Google Scholar
• Rubin P, Finkelstein J, Shapiro D. 1992. Molecular biology mechanisms in the radiation induction of pulmonary injury syndromes: interrelationship between the alveolar macrophage and septal fibroblast. Int J Radiat Oncol Bio Phys. 24:93–101.
   PubMed Web of Science ®Google Scholar
• Rubin P, Johnston CJ, Williams JP, McDonald S, Finkelstein J. 1995. A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys. 33:99–109.
   PubMed Web of Science ®Google Scholar
• Sakai Y, Yamamori T, Yoshikawa Y, Bo T, Suzuki M, Yamamoto K, Ago T, Inanami O. 2018. Nadph oxidase 4 mediates ros production in radiation-induced senescent cells and promotes migration of inflammatory cells. Free Radic Res. 52:92–102.
   PubMed Web of Science ®Google Scholar
• Salama R, Sadaie M, Hoare M, Narita M. 2014. Cellular senescence and its effector programs. Genes Dev. 28:99–114.
   PubMed Web of Science ®Google Scholar
• Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S. 2004. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem. 73:39–85.
   PubMed Web of Science ®Google Scholar
• Schaue D, Kachikwu EL, McBride WH. 2012. Cytokines in radiobiological responses: a review. Radiat Res. 178:505–523.
   PubMed Web of Science ®Google Scholar
• Schaue D, McBride WH. 2010. Links between innate immunity and normal tissue radiobiology. Radiat Res. 173:406–417.
   PubMed Web of Science ®Google Scholar
• Schultz LB, Chehab NH, Malikzay A, Halazonetis TD. 2000. P53 binding protein 1 (53bp1) is an early participant in the cellular response to DNA double strand breaks. J Cell Biol. 151:1381–1390.
   PubMed Web of Science ®Google Scholar
• Sharplin J, Franko A. 1989. A quantitative histological study of strain-dependent differences in the effects of irradiation on mouse lung during the intermediate and late phases. Radiat Res. 119:15–31.
   PubMed Web of Science ®Google Scholar
• Sime PJ, Xing Z, Graham FL, Csaky KG, Gauldie J. 1997. Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. J Clin Invest. 100:768–776.
   PubMed Web of Science ®Google Scholar
• Sisson TH, Mendez M, Choi K, Subbotina N, Courey A, Cunningham A, Dave A, Engelhardt JF, Liu X, White ES, et al. 2010. Targeted injury of type ii alveolar epithelial cells induces pulmonary fibrosis. Am J Respir Crit Care Med. 181:254–263.
   PubMed Web of Science ®Google Scholar
• Snyder JC, Reynolds SD, Hollingsworth JW, Li Z, Kaminski N, Stripp BR. 2010. Clara cells attenuate the inflammatory response through regulation of macrophage behavior. Am J Respir Cell Mol Biol. 42:161–171.
   PubMed Web of Science ®Google Scholar
• Spagnolo P, Wells AU, Collard HR. 2015. Pharmacological treatment of idiopathic pulmonary fibrosis: an update. Drug Discov Today. 0(0):1–11.
   Google Scholar
• Specks U, Martin WJ, Rohrbach MS. 1990. Bronchoalveolar lavage fluid angiotensin-converting enzyme in interstitial lung diseases. Am Rev Respir Dis. 141:117–123.
   PubMed Web of Science ®Google Scholar
• Spitz D, Azzam E, Li JJ, Gius D. 2004. Metabolic oxidation reduction reactions and cellular responses to ionizing radation: a unifying concept in stress biology. Cancer Metastasis Rev. 23:311–322.
   PubMed Web of Science ®Google Scholar
• Sternlicht MD, Wirkner U, Bickelhaupt S, Lopez Perez R, Tietz A, Lipson KE, Seeley TW, Huber PE. 2018. Radiation-induced pulmonary gene expression changes are attenuated by the ctgf antibody pamrevlumab. Respir Res. 19(1):14.
   PubMedGoogle Scholar
• Stone HB, Coleman CN, Anscher MS, McBride WH. 2003. Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol. 4:529–536.
   PubMed Web of Science ®Google Scholar
• Sun F, Sun H, Zheng X, Yang G, Gong N, Zhou H, Wang S, Cheng Z, Ma H. 2018. Angiotensin-converting enzyme inhibitors decrease the incidence of radiation-induced pneumonitis among lung cancer patients: a systematic review and meta-analysis. J Cancer. 9:2123.
   PubMed Web of Science ®Google Scholar
• Tada H, Ogushi F, Tani K, Nishioka Y, Miyata J-y, Sato K, Asano T, Sone S. 2003. Increased binding and chemotactic capacities of pdgf-bb on fibroblasts in radiation pneumonitis. Radiat Res. 159:805–811.
   PubMed Web of Science ®Google Scholar
• Thornton SC, Walsh BJ, Bennett S, Robbins JM, Foulcher E, Morgan GW, Penny R, Breit SN. 1996. Both in vitro and in vivo irradiation are associated with induction of macrophage-derived fibroblast growth factors. Clin Exp Immunol. 103:67–73.
   PubMed Web of Science ®Google Scholar
• Travis EL. 1980. The sequence of histological changes in mouse lungs after single doses of x rays. Int J Radiat Oncol Biol Phys. 6:345–347.
   PubMed Web of Science ®Google Scholar
• Turgut NH, Kara H, Elagoz S, Deveci K, Gungor H, Arslanbas E. 2016. The protective effect of naringin against bleomycin-induced pulmonary fibrosis in wistar rats. Pulm Med. 2016:7601393.
   PubMed Web of Science ®Google Scholar
• Vallée A, Lecarpentier Y, Guillevin R, Vallée J. 2017. Interactions between tgf-β1, canonical WNT/β-catenin pathway and PPAR γ in radiation-induced fibrosis. Oncotarget. 8:90579–90604.
   PubMedGoogle Scholar
• Verhaegen F, Granton P, Tryggestad E. 2011. Small animal radiotherapy research platforms. Phys Med Biol. 56:R55.
   PubMed Web of Science ®Google Scholar
• Vujaskovic Z, Feng Q-F, Rabbani ZN, Anscher MS, Samulski TV, Brizel DM. 2002. Radioprotection of lungs by amifostine is associated with reduction in profibrogenic cytokine activity. Radiat Res. 157:656–660.
   PubMed Web of Science ®Google Scholar
• Wang BZ, Wang LP, Han H, Cao FL, Li GY, Xu JL, Wang XW, Wang LX. 2014. Interleukin-17a antagonist attenuates radiation-induced lung injuries in mice. Exp Lung Res. 40:77–85.
   PubMed Web of Science ®Google Scholar
• Ward WF, Kim YT, Molteni A, Solliday NH. 1988. Radiation-induced pulmonary endothelial dysfunction in rats: modification by an inhibitor of angiotensin converting enzyme. Int J Radiat Oncol Biol Phys. 15:135–140.
   PubMed Web of Science ®Google Scholar
• Werner E, Wang H, Doetsch PW. 2015. Role of pro-inflammatory cytokines in radiation-induced genomic instability in human bronchial epithelial cells. Radiat Res. 184:621–629.
   PubMed Web of Science ®Google Scholar
• Werner E, Wang Y, Doetsch PW. 2017. A single exposure to low- or high-let radiation induces persistent genomic damage in mouse epithelial cells in vitro and in lung tissue. Radiat Res. 188:373–380.
   PubMed Web of Science ®Google Scholar
• Westbury CB, Yarnold JR. 2012. Radiation fibrosis-current clinical and therapeutic perspectives. Clin Oncol (R Coll Radiol). 24:657–672.
   PubMed Web of Science ®Google Scholar
• Williams JP, Calvi L, Chakkalakal JV, Finkelstein JN, O'Banion MK, Puzas E. 2016. Addressing the symptoms or fixing the problem? Developing countermeasures against normal tissue radiation injury. Radiat Res. 186:1–16.
   PubMed Web of Science ®Google Scholar
• Williams JP, Hernady E, Johnston CJ, Reed CM, Fenton B, Okunieff P, Finkelstein JN. 2004. Effect of administration of lovastatin on the development of late pulmonary effects after whole-lung irradiation in a murine model. Radiat Res. 161:560–567.
   PubMed Web of Science ®Google Scholar
• Williams JP, Johnston CJ, Finkelstein J. 2010. Treatment for radiation-induced pulmonary late effects: spoiled for choice or looking in the wrong direction?. Curr Drug Targets. 11:1386–1394.
   PubMed Web of Science ®Google Scholar
• Williams JP, Newhauser W. 2018. Normal tissue damage: its importance, history and challenges for the future. Bjr. 91:20180048.
   Google Scholar
• Williams JP, Brown SL, Georges GE, Hauer-Jensen M, Hill RP, Huser AK, Kirsch DG, Macvittie TJ, Mason KA, Medhora MM, et al. 2010. Animal models for medical countermeasures to radiation exposure. Radiat Res. 173:557–578.
   PubMed Web of Science ®Google Scholar
• Wirsdorfer F, Jendrossek V. 2016. The role of lymphocytes in radiotherapy-induced adverse late effects in the lung. Front Immunol. 7:591.
   PubMed Web of Science ®Google Scholar
• Witte L, Fuks Z, Haimovitz-Friedman A, Vlodavsky I, Goodman DS, Eldor A. 1989. Effects of irradiation on the release of growth factors from cultured bovine, porcine, and human endothelial cells. Cancer Res. 49:5066–5072.
   PubMed Web of Science ®Google Scholar
• Wynn TA, Barron L. 2010. Macrophages: master regulators of inflammation and fibrosis. Semin Liver Dis. 30:245.
   PubMed Web of Science ®Google Scholar
• Xu L, Xiong S, Guo R, Yang Z, Wang Q, Xiao F, Wang H, Pan X, Zhu M. 2014. Transforming growth factor β3 attenuates the development of radiation-induced pulmonary fibrosis in mice by decreasing fibrocyte recruitment and regulating IFN-γ/IL-4 balance. Immunol Lett. 162:27–33.
   PubMed Web of Science ®Google Scholar
• Xu P-T, Maidment BW, Antonic V, Jackson IL, Das S, Zodda A, Zhang X, Seal S, Vujaskovic Z. 2016. Cerium oxide nanoparticles: a potential medical countermeasure to mitigate radiation-induced lung injury in cba/j mice. Radiat Res. 185:516–526.
   PubMed Web of Science ®Google Scholar
• Yahyapour R, Motevaseli E, Rezaeyan A, Abdollahi H, Farhood B, Cheki M, Rezapoor S, Shabeeb D, Musa A, Najafi M. 2018. Reduction–oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics. Clin Transl Oncol. 20:975–988.
   PubMed Web of Science ®Google Scholar
• Yarnold J, Brotons MC. 2010. Pathogenetic mechanisms in radiation fibrosis. Radiother Oncol. 97:149–161.
   PubMed Web of Science ®Google Scholar
• Yatera K, Morimoto Y, Kim H-N, Myojo T, Mukae H. 2011. Foam cell formation of alveolar macrophages in clara cell ablated mice inhaling crystalline silica. Inhal Toxicol. 23:736–744.
   PubMed Web of Science ®Google Scholar
• Yona S, Jung S. 2010. Monocytes: subsets, origins, fates and functions. Curr Opin Hematol. 17:53–59.
   PubMed Web of Science ®Google Scholar
• Yoshida M, Whitsett JA. 2006. Alveolar macrophages and emphysema in surfactant protein‐d‐deficient mice. Respirology. 11:S37–S40.
   PubMed Web of Science ®Google Scholar
• Zhang H, Han G, Liu H, Chen J, Ji X, Zhou F, Zhou Y, Xie C. 2011. The development of classically and alternatively activated macrophages has different effects on the varied stages of radiation-induced pulmonary injury in mice. J Radiat Res. 52:717–726.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Zhang X, Rabbani ZN, Jackson IL, Vujaskovic Z. 2012. Oxidative stress mediates radiation lung injury by inducing apoptosis. Int J Radiat Oncol Biol Phys. 83:740–748.
   PubMed Web of Science ®Google Scholar
• Zhang R, Ghosh SN, Zhu D, North PE, Fish BL, Morrow NV, Lowry T, Nanchal R, Jacobs ER, Moulder JE, et al. 2008. Structural and functional alterations in the rat lung following whole thoracic irradiation with moderate doses: injury and recovery. Int J Radiat Biol. 84:487–497.
   PubMed Web of Science ®Google Scholar
• Zhao W, Robbins M. 2009. Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: therapeutic implications. Curr Med Chem. 16:130–143.
   PubMed Web of Science ®Google Scholar
• Zhou C, Jones B, Moustafa M, Schwager C, Bauer J, Yang B, Cao L, Jia M, Mairani A, Chen M, et al. 2017. Quantitative assessment of radiation dose and fractionation effects on normal tissue by utilizing a novel lung fibrosis index model. Radiat Oncol. 12:172.
   PubMed Web of Science ®Google Scholar