De novo expression of fetal ED-A+ fibronectin and B+ tenascin-C splicing variants in human cardiac allografts: potential impact for targeted therapy of rejection

详细信息    查看全文

• 作者：Marcus Franz ; Monika Matusiak-Brückner ; Petra Richter…
• 关键词：ED ; A+ fibronectin ; B+ tenascin ; C ; Cardiac rejection ; Inflammation ; Targeted therapy
• 刊名：Journal of Molecular Histology
• 出版年：2014
• 出版时间：October 2014
• 年：2014
• 卷：45
• 期：5
• 页码：519-532
• 全文大小：3,573 KB
• 参考文献：1. Armstrong AT, Binkley PF, Baker PB, Myerowitz PD, Leier CV (1998) Quantitative investigation of cardiomyocyte hypertrophy and myocardial fibrosis over 6?years after cardiac transplantation. J Am Coll Cardiol 32:704-10 CrossRef
  2. Baldinger A et al (2011) Comparative analysis of oncofetal fibronectin and tenascin-C expression in right atrial auricular and left ventricular human cardiac tissue from patients with coronary artery disease and aortic valve stenosis. Histochem Cell Biol 135:427-41. doi:10.1007/s00418-011-0809-z CrossRef
  3. Berndt A, Borsi L, Hyckel P, Kosmehl H (2001) Fibrillary co-deposition of laminin-5 and large unspliced tenascin-C in the invasive front of oral squamous cell carcinoma in vivo and in vitro. J Cancer Res Clin Oncol 127:286-92 CrossRef
  4. Booth AJ et al (2012) Recipient-derived EDA fibronectin promotes cardiac allograft fibrosis. J Pathol 226:609-18. doi:10.1002/path.3010 CrossRef
  5. Borsi L et al (1987) Monoclonal antibodies in the analysis of fibronectin isoforms generated by alternative splicing of mRNA precursors in normal and transformed human cells. J Cell Biol 104:595-00 CrossRef
  6. Borsi L, Balza E, Gaggero B, Allemanni G, Zardi L (1995) The alternative splicing pattern of the tenascin-C pre-mRNA is controlled by the extracellular pH. J Biol Chem 270:6243-245 CrossRef
  7. Cale R, Almeida M, Goncalves P, Rebocho MJ, Raposo L, Teles R, Mendes M (2012) Complications of endomyocardial biopsy after heart transplantation: a lesser evil. Rev Port Cardiol 31:159-62. doi:10.1016/j.repc.2011.12.006
  8. Casi G, Neri D (2012) Antibody-drug conjugates: basic concepts, examples and future perspectives. J Controll Release 161:422-28. doi:10.1016/j.jconrel.2012.01.026 CrossRef
  9. Clausell N, Butany J, Molossi S, Lonn E, Gladstone P, Rabinovitch M, Daly PA (1995) Abnormalities in intramyocardial arteries detected in cardiac transplant biopsy specimens and lack of correlation with abnormal intracoronary ultrasound or endothelial dysfunction in large epicardial coronary arteries. J Am Coll Cardiol 26:110-19 CrossRef
  10. Coito AJ, Binder J, de Sousa M, Kupiec-Weglinski JW (1994) The expression of extracellular matrix proteins during accelerated rejection of cardiac allografts in sensitized rats. Transplantation 57:599-05 CrossRef
  11. Coito AJ, Brown LF, Peters JH, Kupiec-Weglinski JW, Van de Water L (1997) Expression of fibronectin splicing variants in organ transplantation: a differential pattern between rat cardiac allografts and isografts. Am J Pathol 150:1757-772
  12. Coito AJ, de Sousa M, Kupiec-Weglinski JW (2000) Fibronectin in immune responses in organ transplant recipients. Dev Immunol 7:239-48 CrossRef
  13. Coito AJ, Kato H, Azimi R, Kupiec-Weglinski JW (2001) Chronic allograft rejection versus tolerance: a critical role for EIIIA(+) fibronectin. Transpl Proc 33:526-27 CrossRef
  14. Costanzo MR et al (2010) The international society of heart and lung transplantation guidelines for the care of heart transplant recipients. J Heart Lung Transplant 29:914-56. doi:10.1016/j.healun.2010.05.034 CrossRef
  15. Costello JP, Mohanakumar T, Nath DS (2013) Mechanisms of chronic cardiac allograft rejection. Tex Heart Inst J 40:395-99
  16. Erba PA et al (2012) Radioimmunotherapy with radretumab in patients with relapsed hematologic malignancies. J Nucl Med 53:922-27. doi:10.2967/jnumed.111.101006 CrossRef
  17. Fiechter M, Frey K, Fugmann T, Kaufmann PA, Neri D (2011) Comparative in vivo analysis of the atherosclerotic plaque targeting properties of eight human monoclonal antibodies. Atherosclerosis 214:325-30. doi:10.1016/j.atherosclerosis.2010.11.027 CrossRef
  18. Franz M et al (2007) A quantitative co-localization analysis of large unspliced tenascin-C(L) and laminin-5/gamma2-chain in basement membranes of oral squamous cell carcinoma by confocal laser scanning microscopy. J Oral Pathol Med 36:6-1. doi:10.1111/j.1600-0714.2006.00492.x CrossRef
  19. Franz M et al (2009) Serum levels of large tenascin-C variants, matrix metalloproteinase-9, and tissue inhibitors of matrix metalloproteinases in concentric versus eccentric left ventricular hypertrophy. Eur J Heart Fail 11:1057-062. doi:10.1093/eurjhf/hfp128 CrossRef
  20. Franz M et al (2010a) Changes in extra cellular matrix remodelling and re-expression of fibronectin and tenascin-C splicing variants in human myocardial tissue of the right atrial auricle: implications for a targeted therapy of cardiovascular diseases using human SIP format antibodies. J Mol Histol 41:39-0. doi:10.1007/s10735-010-9260-z CrossRef
  21. Franz M et al (2010b) Extra cellular matrix remodelling after heterotopic rat heart transplantation: gene expression profiling and involvement of ED-A+ fibronectin, alpha-smooth muscle actin and B+ tenascin-C in chronic cardiac allograft rejection. Histochem Cell Biol 134:503-17. doi:10.1007/s00418-010-0750-6 CrossRef
  22. Franz M et al (2011) Expression of extra domain a containing fibronectin in chronic cardiac allograft rejection. J Heart Lung Transplant 30:86-4. doi:10.1016/j.healun.2010.08.015 CrossRef
  23. Franz M, Neri D, Berndt A (2012) Chronic cardiac allograft rejection: critical role of ED-A(+) fibronectin and implications for targeted therapy strategies. J Pathol 226:557-61. doi:10.1002/path.3968 CrossRef
  24. Franz M et al (2013) Selective imaging of chronic cardiac rejection using a human antibody specific to the alternatively spliced EDA domain of fibronectin. J Heart Lung Transplant 32:641-50. doi:10.1016/j.healun.2013.04.003 CrossRef
  25. Gabler U et al (1996) Matrix remodelling in dilated cardiomyopathy entails the occurrence of oncofetal fibronectin molecular variants. Heart 75:358-62 CrossRef
  26. Glukhova MA, Frid MG, Shekhonin BV, Vasilevskaya TD, Grunwald J, Saginati M, Koteliansky VE (1989) Expression of extra domain a fibronectin sequence in vascular smooth muscle cells is phenotype dependent. J Cell Biol 109:357-66 CrossRef
  27. Gutbrodt KL et al (2013) Antibody-based delivery of interleukin-2 to neovasculature has potent activity against acute myeloid leukemia. Sci Transl Med 5:201ra118. doi:10.1126/scitranslmed.3006221 CrossRef
  28. Hamlin SK, Villars PS, Kanusky JT, Shaw AD (2004) Role of diastole in left ventricular function, II: diagnosis and treatment. Am J Crit Care, 13:453-66; quiz 467-58
  29. Hemmerle T, Neri D (2013) The antibody-based targeted delivery of interleukin-4 and 12 to the tumor neovasculature eradicates tumors in three mouse models of cancer International journal of cancer Journal international du cancer doi:10.1002/ijc.28359
  30. Heuveling DA et al (2013) Phase 0 microdosing PET study using the human mini antibody F16SIP in head and neck cancer patients. J Nucl Med 54:397-01. doi:10.2967/jnumed.112.111310 CrossRef
  31. Hiemann NE, Wellnhofer E, Knosalla C, Lehmkuhl HB, Stein J, Hetzer R, Meyer R (2007) Prognostic impact of microvasculopathy on survival after heart transplantation: evidence from 9713 endomyocardial biopsies. Circulation 116:1274-282. doi:10.1161/CIRCULATIONAHA.106.647149 CrossRef
  32. Imanaka-Yoshida K et al (2001) Tenascin-C modulates adhesion of cardiomyocytes to extracellular matrix during tissue remodeling after myocardial infarction. Lab Invest 81:1015-024 CrossRef
  33. Imanaka-Yoshida K et al (2002) Tenascin-C is a useful marker for disease activity in myocarditis. J Pathol 197:388-94. doi:10.1002/path.1131 CrossRef
  34. Jones FS, Jones PL (2000) The tenascin family of ECM glycoproteins: structure, function, and regulation during embryonic development and tissue remodeling. Dev Dyn 218:235-59. doi:10.1002/(SICI)1097-0177(200006)218:2<235:AID-DVDY2>3.0.CO;2-G CrossRef
  35. Kobashigawa JA et al (2013) Correlation between myocardial fibrosis and restrictive cardiac physiology in patients undergoing retransplantation. Clin Transplant. doi:10.1111/ctr.12250
  36. Minear MA et al (2011) Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease. Hum Genet 129:641-54. doi:10.1007/s00439-011-0959-z CrossRef
  37. Papadia F et al (2013) Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma. J Surg Oncol 107:173-79. doi:10.1002/jso.23168 CrossRef
  38. Pasche N, Neri D (2012) Immunocytokines: a novel class of potent armed antibodies. Drug Discov Today 17:583-90. doi:10.1016/j.drudis.2012.01.007 CrossRef
  39. Schliemann C, Neri D (2010) Antibody-based vascular tumor targeting Recent results in cancer research. Recent Results Cancer Res 180:201-16. doi:10.1007/978-3-540-78281-0_12 CrossRef
  40. Schwager K, Kaspar M, Bootz F, Marcolongo R, Paresce E, Neri D, Trachsel E (2009) Preclinical characterization of DEKAVIL (F8-IL10), a novel clinical-stage immunocytokine which inhibits the progression of collagen-induced arthritis. Arthritis Res Ther 11:R142. doi:10.1186/ar2814 CrossRef
  41. Schwarzbauer JE, Sechler JL (1999) Fibronectin fibrillogenesis: a paradigm for extracellular matrix assembly. Curr Opin Cell Biol 11:622-27 CrossRef
  42. Serini G, Bochaton-Piallat ML, Ropraz P, Geinoz A, Borsi L, Zardi L, Gabbiani G (1998) The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-beta1. J Cell Biol 142:873-81 CrossRef
  43. Skalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G (1986) A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol 103:2787-796 CrossRef
  44. Stehlik J et al (2012) The registry of the international society for heart and lung transplantation: 29th official adult heart transplant report. J Heart Lung Transplant 31:1052-064. doi:10.1016/j.healun.2012.08.002 CrossRef
  45. Stewart S et al (2005) Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant 24:1710-720. doi:10.1016/j.healun.2005.03.019 CrossRef
  46. Suzuki J, Isobe M, Morishita R, Nagai R (2010) Characteristics of chronic rejection in heart transplantation: important elements of pathogenesis and future treatments. Circ J 74:233-39 CrossRef
  47. Trachsel E, Kaspar M, Bootz F, Detmar M, Neri D (2007) A human mAb specific to oncofetal fibronectin selectively targets chronic skin inflammation in vivo. J Invest Dermatol 127:881-86. doi:10.1038/sj.jid.5700653 CrossRef
  48. Tsunoda T et al (2003) Involvement of large tenascin-C splice variants in breast cancer progression. Am J Pathol 162:1857-867. doi:10.1016/S0002-9440(10)64320-9 CrossRef
  49. Whalley GA, Gamble GD, Doughty RN (2007) The prognostic significance of restrictive diastolic filling associated with heart failure: a meta-analysis. Int J Cardiol 116:70-7. doi:10.1016/j.ijcard.2006.03.032 CrossRef
  50. Zheng W et al (2010) Therapeutic benefits of human mesenchymal stem cells derived from bone marrow after global cerebral ischemia. Brain Res 1310:8-6. doi:10.1016/j.brainres.2009.11.012 CrossRef
  
• 作者单位：Marcus Franz (1)
  Monika Matusiak-Brückner (1)
  Petra Richter (2)
  Katja Grün (1)
  Barbara Ziffels (2)
  Dario Neri (3)
  Hansj?rg Maschek (4)
  Uwe Schulz (5)
  Alexander Pfeil (6)
  Christian Jung (1)
  Hans R. Figulla (1)
  Jan Gummert (5)
  Alexander Berndt (2)
  André Renner (5)
  
  1. Department of Internal Medicine I, Jena University Hospital, Erlanger Allee 101, 07740, Jena, Germany
  2. Institute of Pathology, Jena University Hospital, Jena, Germany
  3. Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland
  4. Institute of Pathology, “Pathologie am Tiergarten- Hannover, Germany
  5. Clinic for Thoracic and Cardiovascular Surgery, Heart Center North Rhine-Westphalia, Ruhr-University of Bochum, Bad Oeynhausen, Germany
  6. Department of Internal Medicine III, Jena University Hospital, Jena, Germany
  
• ISSN：1567-2387

文摘

Management of acute and especially chronic rejection after human cardiac transplantation is still challenging. Chronic rejection, represented by allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) is known to cause severe long-term complications. Rejection associated tissue-remodelling entails the reoccurrence of fetal variants of Fibronectin (Fn) and Tenascin-C (Tn-C), which are virtually absent in adult human organs. In a rat model, an extensive re-expression could be demonstrated for ED-A+ Fn with spatial association to CAV and CIF. Thus, it is of great interest to investigate the cardiac tissue expression and distribution in human samples. From 48 heart transplanted patients, 64 tissue specimens derived from right ventricular biopsies were available. Histopathological analysis was performed according to the International Society for Heart and Lung Transplantation (ISHLT) guidelines for the detection of acute rejection. By immunohistochemistry, protein expression of ED-A+ Fn, B+ Tn-C, alpha-smooth muscle actin, CD31 and CD45 was assessed and analysed semiquantitatively. Co-localisation studies were performed by means of immunofluorescence double labelling. Histopathological analysis of the 64 samples revealed different ISHLT grades (0R in 36 cases, 1R in 20 cases and 2R in 8 cases). There was a distinct and quantitatively relevant re-occurrence of ED-A+ Fn and B+ Tn-C in most samples. Semi-quantitative evaluation did not show any correlation to the acute rejection grade for all markers. Interestingly, significant correlations to the extent of inflammation could be shown for ED-A+ Fn (r?=?0.442, p?=?0.000) and B+ Tn-C (r?=?0.408, p?=?0.001) as well as between both proteins (r?=?0.663, p?=?0.000). A spatial association of ED-A+ Fn and B+ Tn-C to CAV and CIF could be demonstrated. A relevant re-occurrence of ED-A+ Fn and B+ Tn-C following human heart transplantation could be demonstrated with spatial association to signs of rejection and a significant correlation to tissue inflammation. These data might contribute to the identification of novel biomarkers reflecting the rejection process and to the development of promising strategies to image, prevent or treat cardiac rejection.