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Published in: Inflammation Research 1/2013

01-01-2013 | Original Research Paper

Fractionated irradiations lead to chronic allergic airway inflammation through increasing the influx of macrophages

Authors: Hae-Ran Park, Sung-Kee Jo, Dong-Kyung Yu, Uhee Jung

Published in: Inflammation Research | Issue 1/2013

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Abstract

Objective

In our previous study, repeated irradiations showed persistent depression of immune response, especially Th1-related immune response. Here, we hypothesized and determined that irradiation may exacerbate development of allergic airway inflammation.

Methods

C57BL/6 mice were irradiated repeatedly at 1 Gy or 0.5 Gy. At 6 months after irradiation, mice were sensitized and challenged short-term with OVA. Antigen-specific immunoglobulins, the percentages of inflammatory cells, chemokine expression, cytokine levels, and collagen deposition were tested.

Results

In irradiated mice, IgG2a in serum was lower when compared with that of control mice, while IgG1 was significantly higher. Interestingly, the percentages of macrophages in bronchoalveolar lavage fluid (BALF) and the lung of irradiated mice were significantly higher. Conversely, the percentages of neutrophil were significantly lower in BALF of irradiated mice. In the lung of irradiated mice, MCP-1 and IP-10 for attraction of macrophages showed the higher expression level, but KC expression for neutrophils showed no difference. Next, TGF-β1 and IL-17A in BALF were higher in irradiated mice. In addition, phosphorylated-Smad2/3 was increased in irradiated mice. Finally, the deposition of collagen was increased in irradiated mice.

Conclusion

Our study showed that fractionated irradiation lead to the chronic allergic airway inflammation through increasing the influx of macrophages and active TGF-β levels.
Literature
1.
go back to reference Safwat A. The role of low-dose total body irradiation in treatment of non-Hodgkin’s lymphoma: a new look at an old method. Radiother Oncol. 2000;56:1–8.PubMedCrossRef Safwat A. The role of low-dose total body irradiation in treatment of non-Hodgkin’s lymphoma: a new look at an old method. Radiother Oncol. 2000;56:1–8.PubMedCrossRef
2.
go back to reference Tago F, Tsukimoto M, Nakatsukasa H, Kojima S. Repeated 0.5 Gy gamma irradiation attenuates autoimmune disease in MRL-lpr/lpr Mice with suppression of CD3+CD4-CD8-B220+ T-cell proliferation and with up-regulation of CD4+CD25+Foxop3+ regulatory T cells. Radiat Res. 2008;169:59–66.PubMedCrossRef Tago F, Tsukimoto M, Nakatsukasa H, Kojima S. Repeated 0.5 Gy gamma irradiation attenuates autoimmune disease in MRL-lpr/lpr Mice with suppression of CD3+CD4-CD8-B220+ T-cell proliferation and with up-regulation of CD4+CD25+Foxop3+ regulatory T cells. Radiat Res. 2008;169:59–66.PubMedCrossRef
3.
go back to reference Tsukimoto M, Nakatsukasa H, Sugawara K, Yamashita K, Kojima S. Repeated 0.5-Gy γ irradiation attenuates experimental autoimmune encephalomyelitis with up-regulation of regulatory T cells and suppression of IL-17 production. Radiat Res. 2008;170:429–36.PubMedCrossRef Tsukimoto M, Nakatsukasa H, Sugawara K, Yamashita K, Kojima S. Repeated 0.5-Gy γ irradiation attenuates experimental autoimmune encephalomyelitis with up-regulation of regulatory T cells and suppression of IL-17 production. Radiat Res. 2008;170:429–36.PubMedCrossRef
4.
go back to reference Luckey TD. Physiological benefits from low leves of ionizing radiation. Health Phys. 1982;43:771–89.PubMedCrossRef Luckey TD. Physiological benefits from low leves of ionizing radiation. Health Phys. 1982;43:771–89.PubMedCrossRef
5.
go back to reference Yonezawa M, Misonoh J, Hosokawa Y. Two types of X-ray induced radioresistance in mice: presence of 4 dose ranges with distinct biological effects. Mutat Res. 1996;358:237–43.PubMedCrossRef Yonezawa M, Misonoh J, Hosokawa Y. Two types of X-ray induced radioresistance in mice: presence of 4 dose ranges with distinct biological effects. Mutat Res. 1996;358:237–43.PubMedCrossRef
6.
go back to reference Kojima S, Ishida H, Takahashi M, Yamaoka K. Elevation of glutathione induced by low-dose gamma rays and its involvement in increased natural killer activity. Radiat Res. 2002;157:275–80.PubMedCrossRef Kojima S, Ishida H, Takahashi M, Yamaoka K. Elevation of glutathione induced by low-dose gamma rays and its involvement in increased natural killer activity. Radiat Res. 2002;157:275–80.PubMedCrossRef
7.
go back to reference Lee YJ, Ducoff HS. Radiation factors and their influence on induction of oxygen resistance. Radiat Res. 1989;117:158–62.PubMedCrossRef Lee YJ, Ducoff HS. Radiation factors and their influence on induction of oxygen resistance. Radiat Res. 1989;117:158–62.PubMedCrossRef
8.
go back to reference Park HR, Jo SK, Eom HS. Chronic effects of single and fractionated γ-irradiation on an impairment of Th1-related immune response. Int J Radiat Biol. 2011;87:534–43.PubMedCrossRef Park HR, Jo SK, Eom HS. Chronic effects of single and fractionated γ-irradiation on an impairment of Th1-related immune response. Int J Radiat Biol. 2011;87:534–43.PubMedCrossRef
9.
go back to reference Romagnani S, Kapsenberg M, Radbruch A, Adorini L. Th1 and Th2 cells. Res Immunol. 1989;149:871–3.CrossRef Romagnani S, Kapsenberg M, Radbruch A, Adorini L. Th1 and Th2 cells. Res Immunol. 1989;149:871–3.CrossRef
10.
go back to reference McMillan SJ, Lloyd CM. Prolonged allergen challenge in mice leads to persistent airway remodelling. Clin Exp Allergy. 2004;34:497–507.PubMedCrossRef McMillan SJ, Lloyd CM. Prolonged allergen challenge in mice leads to persistent airway remodelling. Clin Exp Allergy. 2004;34:497–507.PubMedCrossRef
11.
go back to reference Palmans E, Kips CJ, Pauwels RA. Prolonged allergen expresure induces structural airway changes in sensitized rats. Am J Respir Crit Care Med. 2000;161:627–35.PubMed Palmans E, Kips CJ, Pauwels RA. Prolonged allergen expresure induces structural airway changes in sensitized rats. Am J Respir Crit Care Med. 2000;161:627–35.PubMed
12.
go back to reference Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Cri Care Med. 2000;161:1720–45. Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Cri Care Med. 2000;161:1720–45.
13.
go back to reference Wang Q, Li H, Zhang Z, Yao Y, Zhou J. Prolonged ovalbumin challenge facilitates Th17 polarization in sensitized mice. Inflamm Res. 2010;59:561–9.PubMedCrossRef Wang Q, Li H, Zhang Z, Yao Y, Zhou J. Prolonged ovalbumin challenge facilitates Th17 polarization in sensitized mice. Inflamm Res. 2010;59:561–9.PubMedCrossRef
14.
go back to reference Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. TGFbeta in the context of an inflammatory cytokine milieu supports denovo differentiation of IL-17-producing T cells. Immunity. 2006;24:179–89.PubMedCrossRef Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. TGFbeta in the context of an inflammatory cytokine milieu supports denovo differentiation of IL-17-producing T cells. Immunity. 2006;24:179–89.PubMedCrossRef
15.
go back to reference Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441:235–8.PubMedCrossRef Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441:235–8.PubMedCrossRef
16.
go back to reference Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT. Transforming growth factor-β induces development of the TH-17 lineage. Nature. 2006;441:231–4.PubMedCrossRef Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT. Transforming growth factor-β induces development of the TH-17 lineage. Nature. 2006;441:231–4.PubMedCrossRef
17.
go back to reference Letterio JJ, Roberts AB. Regulation of immune responses by TGF-β. Annu Rev Immunol. 1998;16:137–61.PubMedCrossRef Letterio JJ, Roberts AB. Regulation of immune responses by TGF-β. Annu Rev Immunol. 1998;16:137–61.PubMedCrossRef
18.
go back to reference Bartram U, Speer CP. The role of transforming growth factor-β in lung development and disease. Chest. 2004;125:754–65.PubMedCrossRef Bartram U, Speer CP. The role of transforming growth factor-β in lung development and disease. Chest. 2004;125:754–65.PubMedCrossRef
19.
go back to reference Heldin CH, Miyazono K, ten Dijke P. TGF-beta signaling from cell membrane to nucleus through SMAD proteins. Nature. 1997;390:465–71.PubMedCrossRef Heldin CH, Miyazono K, ten Dijke P. TGF-beta signaling from cell membrane to nucleus through SMAD proteins. Nature. 1997;390:465–71.PubMedCrossRef
20.
go back to reference Park HR, Jo SK, Paik SG. Factors effecting the Th2-like immune response after gamma-irradiation: low production of IL-12 heterodimer in antigen-presenting cells and small expression of the IL-12 receptor in T cells. Int J Radiat Biol. 2005;81:221–31.PubMedCrossRef Park HR, Jo SK, Paik SG. Factors effecting the Th2-like immune response after gamma-irradiation: low production of IL-12 heterodimer in antigen-presenting cells and small expression of the IL-12 receptor in T cells. Int J Radiat Biol. 2005;81:221–31.PubMedCrossRef
21.
go back to reference Assoian RK, Fleurdelys BE, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB. Expression and secretion of type β transforming growth factor by activated human macrophages. Proc Natl Acad Sci USA. 1987;84:6020–4.PubMedCrossRef Assoian RK, Fleurdelys BE, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB. Expression and secretion of type β transforming growth factor by activated human macrophages. Proc Natl Acad Sci USA. 1987;84:6020–4.PubMedCrossRef
22.
go back to reference Dorr W, Hendry JH. Consequential late effects in normal tissues. Radiother Oncol. 2001;61:223–31.PubMedCrossRef Dorr W, Hendry JH. Consequential late effects in normal tissues. Radiother Oncol. 2001;61:223–31.PubMedCrossRef
23.
go back to reference Jung H, Beck-Bornholdt HP, Svoboda V, Alberti W, Herrmann T. Quantification of late complications after radiation therapy. Radiother Oncol. 2001;61:233–46.PubMedCrossRef Jung H, Beck-Bornholdt HP, Svoboda V, Alberti W, Herrmann T. Quantification of late complications after radiation therapy. Radiother Oncol. 2001;61:233–46.PubMedCrossRef
24.
go back to reference Tang C, Inman MD, Rooijen NV, Yang P, Shen H, Matsumoto K, O’Byrne PM. Th type 1-stimulating activity of lung macrophages inhibits Th2-meidated allergic airway inflammation by an IFN-γ-dependent mechanism. J Immunol. 2001;166:1471–81.PubMed Tang C, Inman MD, Rooijen NV, Yang P, Shen H, Matsumoto K, O’Byrne PM. Th type 1-stimulating activity of lung macrophages inhibits Th2-meidated allergic airway inflammation by an IFN-γ-dependent mechanism. J Immunol. 2001;166:1471–81.PubMed
25.
go back to reference Tanay A, Strober S. Opposite effects of total lymphoid irradiation on T cell-dependent and T cell-independent antibody responses. J Immunol. 1984;132:979–84.PubMed Tanay A, Strober S. Opposite effects of total lymphoid irradiation on T cell-dependent and T cell-independent antibody responses. J Immunol. 1984;132:979–84.PubMed
26.
go back to reference Bass H, Mosmann T, Strober S. Evidence for mouse Th1- and Th2-like helper T cells in vivo. Selective reduction of Th1-like cells after total lymphoid irradiation. J Exp Med. 1989;170:1495–511.PubMedCrossRef Bass H, Mosmann T, Strober S. Evidence for mouse Th1- and Th2-like helper T cells in vivo. Selective reduction of Th1-like cells after total lymphoid irradiation. J Exp Med. 1989;170:1495–511.PubMedCrossRef
27.
go back to reference Hayashi T, Kusunoki Y, Hakoda M, Morishita Y, Kubo Y, Maki M, Kasagi F, Kodama K, Macphee DG, Kyoizumi S. Radiation dose-dependent increase in inflammatory response markers in A-bomb survivors. Int J Radiat Biol. 2003;79:129–36.PubMed Hayashi T, Kusunoki Y, Hakoda M, Morishita Y, Kubo Y, Maki M, Kasagi F, Kodama K, Macphee DG, Kyoizumi S. Radiation dose-dependent increase in inflammatory response markers in A-bomb survivors. Int J Radiat Biol. 2003;79:129–36.PubMed
28.
go back to reference Jr WO, Zenewicz LA, Flavell RA. The dual nature of TH17 cells: shifting the focus to function. Nat Immunol. 2010;11:471–6.CrossRef Jr WO, Zenewicz LA, Flavell RA. The dual nature of TH17 cells: shifting the focus to function. Nat Immunol. 2010;11:471–6.CrossRef
29.
go back to reference Temelkovski J, Hogan SP, Shepherd DP, Foster PS, Kumar RK. An improved murine model of asthma: selective sirway inflammation, epithelial lesions and increased methachline responsiveness following chronic exposure to aerosolised allergen. Thorax. 1998;53:849–56.PubMedCrossRef Temelkovski J, Hogan SP, Shepherd DP, Foster PS, Kumar RK. An improved murine model of asthma: selective sirway inflammation, epithelial lesions and increased methachline responsiveness following chronic exposure to aerosolised allergen. Thorax. 1998;53:849–56.PubMedCrossRef
30.
go back to reference Koerner-Rettberg C, Doths S, Stroet A, Schwarze J. Reduced lung function in a chronic asthma model is associated with prolonged inflammation, but independent of peribronchial fibrosis. PLoS ONE. 2008;3:1–10.CrossRef Koerner-Rettberg C, Doths S, Stroet A, Schwarze J. Reduced lung function in a chronic asthma model is associated with prolonged inflammation, but independent of peribronchial fibrosis. PLoS ONE. 2008;3:1–10.CrossRef
31.
go back to reference Mantovani A. Macrophage diversity and polarization: in vivo veritas. Blood. 2006;108:408.CrossRef Mantovani A. Macrophage diversity and polarization: in vivo veritas. Blood. 2006;108:408.CrossRef
32.
go back to reference Varin A, Gordon S. Alternative activation of macrophages: immune function and cellular biology. Immunobiol. 2009;214:630–41.CrossRef Varin A, Gordon S. Alternative activation of macrophages: immune function and cellular biology. Immunobiol. 2009;214:630–41.CrossRef
33.
go back to reference Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010;32:593–604.PubMedCrossRef Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010;32:593–604.PubMedCrossRef
34.
go back to reference Nair MG, Cochrane DW, Allen JE. Macrophages in chronic type 2 inflammation have a novel phenotype characterized by the abundant expression of Ym1 and Fizz1 that can be partly replicated in vitro. Immunol Lett. 2003;85:173–80.PubMedCrossRef Nair MG, Cochrane DW, Allen JE. Macrophages in chronic type 2 inflammation have a novel phenotype characterized by the abundant expression of Ym1 and Fizz1 that can be partly replicated in vitro. Immunol Lett. 2003;85:173–80.PubMedCrossRef
35.
go back to reference Ford AQ, Dasgupta P, Mikhailenko I, Smith EMP, Noben-Trauth N, Deegan AD. Adoptive transfer of IL-4Rα+ macrophages is sufficient to enhance eosinophilic inflammation in a mouse model of allergic lung inflammation. BMC Immunol. 2012;13:6–22.PubMedCrossRef Ford AQ, Dasgupta P, Mikhailenko I, Smith EMP, Noben-Trauth N, Deegan AD. Adoptive transfer of IL-4Rα+ macrophages is sufficient to enhance eosinophilic inflammation in a mouse model of allergic lung inflammation. BMC Immunol. 2012;13:6–22.PubMedCrossRef
Metadata
Title
Fractionated irradiations lead to chronic allergic airway inflammation through increasing the influx of macrophages
Authors
Hae-Ran Park
Sung-Kee Jo
Dong-Kyung Yu
Uhee Jung
Publication date
01-01-2013
Publisher
SP Birkhäuser Verlag Basel
Published in
Inflammation Research / Issue 1/2013
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-012-0547-2

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