Small animal models of experimental obliterative bronchiolitis

American Journal of Respiratory Cell and Molecular Biology

Volumn 48, Issue 6, 2013, Pages 675-684

  Jungraithmayr, Wolfgang ^a   Jang, Jae Hwi ^a   Schrepfer, Sonja ^b,c   Inci, Ilhan ^a   Weder, Walter ^a  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b UNIVERSITY HEART CENTER HAMBURG   (Germany)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Mouse; Obliterative bronchiolitis; Rat; Transplantation

Indexed keywords

ANTIBIOTIC AGENT; AZITHROMYCIN; CLARITHROMYCIN; CYCLOSPORIN A; IMMUNOSUPPRESSIVE AGENT; RAPAMYCIN; TACROLIMUS; CYTOKINE; NITRIC OXIDE;

ANIMAL MODEL; BRONCHIOLITIS OBLITERANS; DRUG MECHANISM; HETEROTOPIC TRANSPLANTATION; HUMAN; INTRAPULMONARY TRACHEAL IMPLANTATION; LUNG GRAFT REJECTION; LUNG TRANSPLANTATION; MESENCHYMAL STEM CELL TRANSPLANTATION; NONHUMAN; ORTHOTOPIC TRACHEAL TRANSPLANTATION; ORTHOTOPIC TRANSPLANTATION; PATHOGENESIS; REVIEW; TRACHEA SURGERY; ANIMAL; DISEASE MODEL; GRAFT REJECTION; IMMUNOLOGY; LUNG; METABOLISM; METHODOLOGY; MOUSE; PATHOLOGY; RAT; RESPIRATORY TRACT MUCOSA; TRACHEA; TRANSPLANTATION;

ANIMALS; BRONCHIOLITIS OBLITERANS; CYTOKINES; DISEASE MODELS, ANIMAL; GRAFT REJECTION; HUMANS; LUNG; LUNG TRANSPLANTATION; MICE; NITRIC OXIDE; RATS; RESPIRATORY MUCOSA; TRACHEA;

MLCS; MLOWN;

EID: 84880987821     PISSN: 10441549     EISSN: 15354989     Source Type: Journal    
DOI: 10.1165/rcmb.2012-0379TR     Document Type: Review

References (94)

1. Burke CM, Theodore J, Dawkins KD, Yousem SA, Blank N, Billingham ME, Van Kessel A, Jamieson SW, Oyer PE, Baldwin JC, et al. Posttransplant obliterative bronchiolitis and other late lung sequelae in human heart-lung transplantation. Chest 1984;86: 824-829.
2. Hertz MI, Jessurun J, King MB, Savik SK, Murray JJ. Reproduction of the obliterative bronchiolitis lesion after heterotopic transplantation of mouse airways. Am J Pathol 1993;142: 1945-1951.
3. Allan JS,Wain JC, Schwarze ML, Houser SL, Benjamin LC, Madsen JC, Sachs DH. Modeling chronic lung allograft rejection in miniature swine. Transplantation 2002;73: 447-453.
4. Boehler A, Chamberlain D, Kesten S, Slutsky AS, Liu M, Keshavjee S. Lymphocytic airway infiltration as a precursor to fibrous obliteration in a rat model of bronchiolitis obliterans. Transplantation 1997;64: 311-317.
5. King MB, Pedtke AC, Levrey-Hadden HL, Hertz MI. Obliterative airway disease progresses in heterotopic airway allografts without persistent alloimmune stimulus. Transplantation 2002;74: 557-562.
6. Chalermskulrat W, Neuringer IP, Brickey WJ, Felix NJ, Randell SH, Ting JP, Aris RM. Hierarchical contributions of allorecognition pathways in chronic lung rejection. Am J Respir Crit Care Med 2003; 167: 999-1007.
7. Neuringer IP, Mannon RB, Coffman TM, Parsons M, Burns K, Yankaskas JR, Aris RM. Immune cells in a mouse airway model of obliterative bronchiolitis. Am J Respir Cell Mol Biol 1998;19: 379-386.
8. Kelly KE, Hertz MI, Mueller DL. T-cell and major histocompatibility complex requirements for obliterative airway disease in heterotopically transplanted murine tracheas. Transplantation 1998;66: 764-771.
9. Ropponen JO, Syrjala SO, Krebs R, Nykanen A, Tikkanen JM, Lemstrom KB. Innate and adaptive immune responses in obliterative airway disease in rat tracheal allografts. J Heart Lung Transplant 2011;30: 707-716.
10. Adams BF, Brazelton T, Berry GJ, Morris RE. The role of respiratory epithelium in a rat model of obliterative airway disease. Transplantation 2000;69: 661-664.
11. Ikonen TS, Brazelton TR, Berry GJ, Shorthouse RS, Morris RE. Epithelial re-growth is associated with inhibition of obliterative airway disease in orthotopic tracheal allografts in non-immunosuppressed rats. Transplantation 2000;70: 857-863.
12. Dosanjh A, Ikonen T, Morris R. Respiratory epithelial expression of integrin alphaVbeta6 in chronic progressive allograft rejection. J Heart Lung Transplant 2004;23: 456-460.
13. Kallio EA, Koskinen PK, Aavik E, Vaali K, Lemstom KB. Role of nitric oxide in experimental obliterative bronchiolitis (chronic rejection) in the rat. J Clin Invest 1997;100: 2984-2994.
14. Salminen US, Maasilta PK, Harjula AL, Romanska HM, Bishop AE, Polak JM. Nitric oxide in the development of obliterative bronchiolitis in a heterotopic pig model. Transplantation 2002;73: 1724-1729.
15. Neurohr C, Huppmann P, Leuschner S, von Wulffen W, Meis T, Leuchte H, Ihle F, Zimmermann G, Baezner C, Hatz R, et al. Usefulness of exhaled nitric oxide to guide risk stratification for bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant 2011;11: 129-137.
16. Koskinen PK, Kallio EA, Krebs R, Lemstrom KB. A dose-dependent inhibitory effect of cyclosporine A on obliterative bronchiolitis of rat tracheal allografts. Am J Respir Crit Care Med 1997;155: 303-312.
17. King MB, Jessurun J, Savik SK, Murray JJ, Hertz MI. Cyclosporine reduces development of obliterative bronchiolitis in a murine heterotopic airway model. Transplantation 1997;63: 528-532.
18. Remund K, Rechsteiner T, Rentsch K, Vogt P, Russi EW, Boehler A. Attenuation of airway obliteration by ciprofloxacin in experimental posttransplant bronchiolitis obliterans. Transplantation 2008;85: 726-731.
19. Fahrni JA, Berry GJ, Morris RE, Rosen GD. Rapamycin inhibits development of obliterative airway disease in a murine heterotopic airway transplant model. Transplantation 1997;63: 533-537.
20. Hollmen M, Tikkanen JM, Nykanen AI, Koskinen PK, Lemstrom KB. Tacrolimus treatment effectively inhibits progression of obliterative airway disease even at later stages of disease development. J Heart Lung Transplant 2008;27: 856-864.
21. Takao M, Gu Y, Shimamoto A, Adachi K, Namikawa S, Yada I. Administration of exogenous interleukin-2 enhances obliterative airway disease in cyclosporine-treated rats following tracheal allografts. Transplant Proc 1999;31: 180-181.
22. Kita Y, Suzuki K, Nogimura H, Takahashi T, Kazui T. CTLA4IG-gene transfection inhibits obliterative airway disease in rats. Ann Thorac Surg 2003;75: 1123-1127.
23. Tikkanen JM, Lemstrom KB, Koskinen PK. Blockade of CD28/B7-2 costimulation inhibits experimental obliterative bronchiolitis in rat tracheal allografts: suppression of helper T cell Type 1-dominated immune response. Am J Respir Crit Care Med 2002;165: 724-729.
24. Shah PD, West EE,Whitlock AB, Orens JB, McDyer JF. CD154 deficiency uncouples allograft CD81 T-cell effector function from proliferation and inhibits murine airway obliteration. Am J Transplant 2009;9: 2697-2706.
25. Yamada A, Konishi K, Cruz GL, Takehara M, Morikawa M, Nakagawa I, Murakami M, Abe T, Todo S, Uede T. Blocking the CD28-B7 T-cell costimulatory pathway abrogates the development of obliterative bronchiolitis in a murine heterotopic airway model. Transplantation 2000;69: 743-749.
26. Kallio EA, Lemstrom KB, Hayry PJ, Ryan US, Koskinen PK. Blockade of complement inhibits obliterative bronchiolitis in rat tracheal allografts. Am J Respir Crit Care Med 2000;161: 1332-1339.
27. Farivar AS, Krishnadasan B, Naidu BV, Woolley SM, Mulligan MS. The role of the beta chemokines in experimental obliterative bronchiolitis. Exp Mol Pathol 2003;75: 210-216.
28. Suga M, Maclean AA, Keshavjee S, Fischer S, Moreira JM, Liu M. RANTES plays an important role in the evolution of allograft transplant-induced fibrous airway obliteration. Am J Respir Crit Care Med 2000;162: 1940-1948.
29. Belperio JA, Keane MP, Burdick MD, Lynch JP III, Xue YY, Berlin A, Ross DJ, Kunkel SL, Charo IF, Strieter RM. Critical role for the chemokine MCP-1/CCR2 in the pathogenesis of bronchiolitis obliterans syndrome. J Clin Invest 2001;108: 547-556.
30. Belperio JA, Keane MP, Burdick MD, Lynch JP III, Xue YY, Li K, Ross DJ, Strieter RM. Critical role for CXCR3 chemokine biology in the pathogenesis of bronchiolitis obliterans syndrome. J Immunol 2002; 169: 1037-1049.
31. Aris RM, Walsh S, Chalermskulrat W, Hathwar V, Neuringer IP. Growth factor upregulation during obliterative bronchiolitis in the mouse model. Am J Respir Crit Care Med 2002;166: 417-422.
32. Kallio EA, Koskinen PK, Aavik E, Buchdunger E, Lemstrom KB. Role of platelet-derived growth factor in obliterative bronchiolitis (chronic rejection) in the rat. Am J Respir Crit Care Med 1999;160: 1324-1332.
33. Tikkanen JM, Hollmen M, Nykanen AI, Wood J, Koskinen PK, Lemstrom KB. Role of platelet-derived growth factor and vascular endothelial growth factor in obliterative airway disease. Am J Respir Crit Care Med 2006;174: 1145-1152.
34. Farivar AS, Mackinnon-Patterson B, Woolley S, Namkung J, Shimamoto A, Verrier ED, Mulligan MS. FR167653 reduces obliterative airway disease in rats. J Heart Lung Transplant 2004;23: 985-992.
35. Farivar AS, Mackinnon-Patterson B, McCourtie AS, Namkung J, Ward PA, Mulligan MS. Obliterative airway disease in rat tracheal allografts requires tumor necrosis factor alpha. Exp Mol Pathol 2005;78: 190-197.
36. Boehler A, Chamberlain D, Xing Z, Slutsky AS, Jordana M, Gauldie J, Liu M, Keshavjee S. Adenovirus-mediated interleukin-10 gene transfer inhibits post-transplant fibrous airway obliteration in an animal model of bronchiolitis obliterans. Hum Gene Ther 1998;9: 541-551.
37. Liu M, Suga M, Maclean AA, St George JA, Souza DW, Keshavjee S. Soluble transforming growth factor-beta Type III receptor gene transfection inhibits fibrous airway obliteration in a rat model of bronchiolitis obliterans. Am J Respir Crit Care Med 2002;165: 419-423.
38. Naidu B, Krishnadasan B, Whyte RI, Warner RL, Ward PA, Mulligan MS. Regulatory role of IL-10 in experimental obliterative bronchiolitis in rats. Exp Mol Pathol 2002;73: 164-170.
39. Tsuchida M, Koike T, Takekubo M, Hirahara H, Hanawa H, Maruyama H, Miyazaki J, Hayashi J. Electroporation-mediated transfer of plasmid DNA encoding IL-10 attenuates orthotopic tracheal allograft stenosis in rats. Transpl Immunol 2008;19: 173-177.
40. Ramirez AM, Takagawa S, Sekosan M, Jaffe HA, Varga J, Roman J. Smad3 deficiency ameliorates experimental obliterative bronchiolitis in a heterotopic tracheal transplantation model. Am J Pathol 2004;165: 1223-1232.
41. Ramirez AM, Shen Z, Ritzenthaler JD, Roman J. Myofibroblast transdifferentiation in obliterative bronchiolitis: TGF-beta signaling through Smad3-dependent and -independent pathways. Am J Transplant 2006;6: 2080-2088.
42. Inaki N, Tsunezuka Y, Kawakami K, Sato H, Takino T, OdaM,Watanabe G. Increased matrix metalloproteinase-2 and membrane Type 1 matrix metalloproteinase activity and expression in heterotopically transplanted murine tracheas. J Heart Lung Transplant 2004;23: 218-227.
43. Khatwa UA, Kleibrink BE, Shapiro SD, Subramaniam M. MMP-8 promotes polymorphonuclear cell migration through collagen barriers in obliterative bronchiolitis. J Leukoc Biol 2010;87: 69-77.
44. Fernandez FG, Campbell LG, Liu W, Shipley JM, Itohara S, Patterson GA, Senior RM, Mohanakumar T, Jaramillo A. Inhibition of obliterative airway disease development in murine tracheal allografts by matrix metalloproteinase-9 deficiency. Am J Transplant 2005;5: 671-683.
45. Lande JD, Dalheimer SL, Mueller DL, Hertz MI, King RA. Gene expression profiling in murine obliterative airway disease. Am J Transplant 2005;5: 2170-2184.
46. Sato M, Hwang DM, Guan Z, Yeung JC, Anraku M, Wagnetz D, Hirayama S,Waddell TK, Liu M, Keshavjee S. Regression of allograft airway fibrosis: the role of MMP-dependent tissue remodeling in obliterative bronchiolitis after lung transplantation. Am J Pathol 2011;179: 1287-1300.
47. Sato M, Liu M, Anraku M, Ogura T, D'Cruz G, Alman BA, Waddell TK, Kim E, Zhang L, Keshavjee S. Allograft airway fibrosis in the pulmonary milieu: a disorder of tissue remodeling. Am J Transplant 2008;8: 517-528.
48. Grove DA, Xu J, Joodi R, Torres-Gonzales E, Neujahr D, Mora AL, Rojas M. Attenuation of early airway obstruction by mesenchymal stem cells in a murine model of heterotopic tracheal transplantation. J Heart Lung Transplant 2011;30: 341-350.
49. Schrepfer S, Deuse T, Hoyt G, Sheikh AY, Hoffmann J, Reichenspurner H, Robbins RC, Pelletier MP. Experimental orthotopic tracheal transplantation: the Stanford technique. Microsurgery 2007;27: 187-189.
50. Genden EM, Boros P, Liu J, Bromberg JS, Mayer L. Orthotopic tracheal transplantation in the murine model. Transplantation 2002;73: 1420-1425.
51. Genden EM, Iskander A, Bromberg JS, Mayer L. The kinetics and pattern of tracheal allograft re-epithelialization. Am J Respir Cell Mol Biol 2003;28: 673-681.
52. Kuo E, Bharat A, Goers T, Chapman W, Yan L, Street T, Lu W, Walter M, Patterson A, Mohanakumar T. Respiratory viral infection in obliterative airway disease after orthotopic tracheal transplantation. Ann Thorac Surg 2006;82: 1043-1050.
53. Bharat A, Kuo E, Saini D, Steward N, Hachem R, Trulock EP, Patterson GA, Meyers BF, Mohanakumar T. Respiratory virus-induced dysregulation of T-regulatory cells leads to chronic rejection. Ann Thorac Surg 2010;90:1637-1644, discussion 1644.
54. Jiang X, Khan MA, Tian W, Beilke J, Natarajan R, Kosek J, Yoder MC, Semenza GL, Nicolls MR. Adenovirus-mediated HIF-1alpha gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection. J Clin Invest 2011;121: 2336-2349.
55. Babu AN, Murakawa T, Thurman JM, Miller EJ, Henson PM, Zamora MR, Voelkel NF, Nicolls MR. Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis. J Clin Invest 2007;117: 3774-3785.
56. Khan MA, Nicolls MR. Complement-mediated microvascular injury leads to chronic rejection. Adv Exp Med Biol 2013;734: 233-246.
57. Minamoto K, Pinsky DJ. Recipient iNOS but not eNOS deficiency reduces luminal narrowing in tracheal allografts. J Exp Med 2002;196: 1321-1333.
58. Lama VN, Harada H, Badri LN, Flint A, Hogaboam CM, McKenzie A, Martinez FJ, Toews GB, Moore BB, Pinsky DJ. Obligatory role for interleukin-13 in obstructive lesion development in airway allografts. Am J Pathol 2006;169: 47-60.
59. Keane MP, Gomperts BN, Weigt S, Xue YY, Burdick MD, Nakamura H, Zisman DA, Ardehali A, Saggar R, Lynch JP III, et al. IL-13 is pivotal in the fibro-obliterative process of bronchiolitis obliterans syndrome. J Immunol 2007;178: 511-519.
60. Dutly AE, Andrade CF, Verkaik R, Kugathasan L, Trogadis J, Liu M, Waddell TK, Stewart DJ, Keshavjee S. A novel model for posttransplant obliterative airway disease reveals angiogenesis from the pulmonary circulation. Am J Transplant 2005;5: 248-254.
61. Sato M, Hirayama S, Lara-Guerra H, Anraku M, Waddell TK, Liu M, Keshavjee S. MMP-dependent migration of extrapulmonary myofibroblast progenitors contributing to posttransplant airway fibrosis in the lung. Am J Transplant 2009;9: 1027-1036.
62. Sato M, Hirayama S, Hwang DM, Lara-Guerra H, Wagnetz D, Waddell TK, Liu M, Keshavjee S. The role of intrapulmonary de novo lymphoid tissue in obliterative bronchiolitis after lung transplantation. J Immunol 2009;182: 7307-7316.
63. Hirayama S, Sato M, Liu M, Loisel-Meyer S, Yeung JC, Wagnetz D, Cypel M, Zehong G, Medin JA, Keshavjee S. Local long-term expression of lentivirally delivered IL-10 in the lung attenuates obliteration of intrapulmonary allograft airways. Hum Gene Ther 2011;22: 1453-1460.
64. Watanabe T, Okada Y, Hoshikawa Y, Eba S, Notsuda H, Watanabe Y, Ohishi H, Sato Y, Kondo T. A potent anti-angiogenic factor, vasohibin-1, ameliorates experimental bronchiolitis obliterans. Transplant Proc 2012; 44: 1155-1157.
65. Asimacopoulos PJ, Molokhia FA, Pegg CA, Norman JC. Lung transplantation in the rat. Transplant Proc 1971;3: 583-585.
66. Tazelaar HD, Prop J, Nieuwenhuis P, Billingham ME, Wildevuur CR. Airway pathology in the transplanted rat lung. Transplantation 1988; 45: 864-869.
67. Romaniuk A, Prop J, Petersen AH, Wildevuur CR, Nieuwenhuis P. Expression of Class II major histocompatibility complex antigens by bronchial epithelium in rat lung allografts. Transplantation 1987;44: 209-214.
68. Uyama T, Winter JB, Groen G, Wildevuur CR, Monden Y, Prop J. Late airway changes caused by chronic rejection in rat lung allografts. Transplantation 1992;54: 809-812.
69. Lee AG, Wagner FM, Giaid A, Chen MF, Hamid Q, Serrick C, Shennib H. Immunohistochemical characterization of inflammatory and proliferative events during chronic rejection in rat lung allografts. Transplantation 1997;64: 465-471.
70. Lee AG, Wagner FM, Chen MF, Serrick C, Giaid A, Shennib H. A novel charcoal-induced model of obliterative bronchiolitis-like lesions: implications of chronic nonspecific airway inflammation in the development of posttransplantation obliterative bronchiolitis. J Thorac Cardiovasc Surg 1998;115: 822-827.
71. Winter JB, Gouw AS, Groen M, Wildevuur C, Prop J. Respiratory viral infections aggravate airway damage caused by chronic rejection in rat lung allografts. Transplantation 1994;57: 418-422.
72. Matsumura Y, Marchevsky A, Zuo XJ, Kass RM, Matloff JM, Jordan SC. Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation. Transplantation 1995;59: 1509-1517.
73. Jungraithmayr W, Kayser G, Haberstroh J, Weder W, Korom S. An experimental approach toward chronic pulmonary allograft rejection: orthotopic lung versus heterotopic tracheal segment transplantation in rats. Transplant Proc 2010;42: 2767-2770.
74. Hirt SW, You XM, Moller F, Boeke K, Starke M, Spranger U, Wottge HU. Development of obliterative bronchiolitis after allogeneic rat lung transplantation: implication of acute rejection and the time point of treatment. J Heart Lung Transplant 1999;18: 542-548.
75. von Susskind-Schwendi M, Ruemmele P, Schmid C, Hirt SW, Lehle K. Lung transplantation in the Fischer 344-Wistar Kyoto strain combination is a relevant experimental model to study the development of bronchiolitis obliterans in the rat. Exp Lung Res 2012;38: 111-123.
76. Zweers N, Petersen AH, van der Hoeven JA, de Haan A, Ploeg RJ, de Leij LF, Prop J. Donor brain death aggravates chronic rejection after lung transplantation in rats. Transplantation 2004;78: 1251-1258.
77. Hirschburger M, Greschus S, Kuchenbuch T, Plotz C, Obert M, Traupe H, Padberg W, Grau V. Lung transplantation in the Fischer 344→Wistar Kyoto rat strain combination is not suitable to study bronchiolitis obliterans. J Heart Lung Transplant 2007;26: 390-398.
78. Wiebe K, Fraund S, Steinmuller C, Steinhoff G. Rat cytomegalovirus and Listeria monocytogenes infection enhance chronic rejection after allogenic rat lung transplantation. Transpl Int 2005;18: 1166-1174.
79. Jungraithmayr W, Vogt P, Inci I, Hillinger S, Arni S, Korom S, Weder W. A model of chronic lung allograft rejection in the rat. Eur Respir J 2010;35: 1354-1363.
80. Li B, Hartwig MG, Appel JZ, Bush EL, Balsara KR, Holzknecht ZE, Collins BH, Howell DN, Parker W, Lin SS, et al. Chronic aspiration of gastric fluid induces the development of obliterative bronchiolitis in rat lung transplants. Am J Transplant 2008;8: 1614-1621.
81. Yasufuku K, Heidler KM, Woods KA, Smith GN Jr, Cummings OW, Fujisawa T, Wilkes DS. Prevention of bronchiolitis obliterans in rat lung allografts by Type V collagen-induced oral tolerance. Transplantation 2002;73: 500-505.
82. Palmer SM, Flake GP, Kelly FL, Zhang HL, Nugent JL, Kirby PJ, Foley JF, Gwinn WM, Morgan DL. Severe airway epithelial injury, aberrant repair and bronchiolitis obliterans develops after diacetyl instillation in rats. PLoS ONE 2011;6:e17644.
83. Jungraithmayr WM, Korom S, Hillinger S, Weder W. A mouse model of orthotopic, single-lung transplantation. J Thorac Cardiovasc Surg 2009;137: 486-491.
84. Okazaki M, Krupnick AS, Kornfeld CG, Lai JM, Ritter JH, Richardson SB, Huang HJ, Das NA, Patterson GA, Gelman AE, et al. A mouse model of orthotopic vascularized aerated lung transplantation. Am J Transplant 2007;7: 1672-1679.
85. Okazaki M, Gelman AE, Tietjens JR, Ibricevic A, Kornfeld CG, Huang HJ, Richardson SB, Lai J, Garbow JR, Patterson GA, et al. Maintenance of airway epithelium in acutely rejected orthotopic vascularized mouse lung transplants. Am J Respir Cell Mol Biol 2007;37: 625-630.
86. Fan L, Benson HL, Vittal R, Mickler EA, Presson R, Fisher AJ, Cummings OW, Heidler KM, Keller MR, Burlingham WJ, et al. Neutralizing IL-17 prevents obliterative bronchiolitis in murine orthotopic lung transplantation. Am J Transplant 2011;11: 911-922.
87. De Vleeschauwer S, Jungraithmayr W, Wauters S, Willems S, Rinaldi M, Vaneylen A, Verleden S, Willems-Widyastuti A, Bracke K, Brusselle G, et al. Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks. PLoS ONE 2012;7:e29802.
88. Xue J, Zhu X, George MP, Myerburg MM, Stoner MW, Pilewski JW, Duncan SR. A human-mouse chimeric model of obliterative bronchiolitis after lung transplantation. Am J Pathol 2011;179: 745-753.
89. Borthwick LA, Parker SM, Brougham KA, Johnson GE, Gorowiec MR, Ward C, Lordan JL, Corris PA, Kirby JA, Fisher AJ. Epithelial to mesenchymal transition (EMT) and airway remodelling after human lung transplantation. Thorax 2009;64: 770-777.
90. Heijink IH, Postma DS, Noordhoek JA, Broekema M, Kapus A. House dust mite-promoted epithelial-to-mesenchymal transition in human bronchial epithelium. Am J Respir Cell Mol Biol 2010;42: 69-79.
91. Sohal SS, Reid D, Soltani A, Ward C, Weston S, Muller HK, Wood- Baker R, Walters EH. Evaluation of epithelial mesenchymal transition in patients with chronic obstructive pulmonary disease. Respir Res 2011;12:130.
92. Gorowiec MR, Borthwick LA, Parker SM, Kirby JA, Saretzki GC, Fisher AJ. Free radical generation induces epithelial-to-mesenchymal transition in lung epithelium via a TGF-beta1-dependent mechanism. Free Radic Biol Med 2012;52: 1024-1032.
93. Borthwick LA, McIlroy EI, Gorowiec MR, Brodlie M, Johnson GE, Ward C, Lordan JL, Corris PA, Kirby JA, Fisher AJ. Inflammation and epithelial to mesenchymal transition in lung transplant recipients: role in dysregulated epithelial wound repair. Am J Transplant 2010; 10: 498-509.
94. Borthwick LA, Sunny SS, Oliphant V, Perry J, Brodlie M, Johnson GE, Ward C, Gould K, Corris PA, De Soyza A, et al. Pseudomonas aeruginosa accentuates epithelial-to-mesenchymal transition in the airway. Eur Respir J 2011;37: 1237-1247.