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Cytokines in the conjunctiva of acute and chronic mucous membrane pemphigoid: An immunohistochemical analysis

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Abstract

The aim of this study was to evaluate the potential role of certain soluble factors in conjunctival scar tissue formation of pemphigoid patients. Epibulbar conjunctival biopsy specimens were taken from patients with acute ulcerative (n = 4), subacute (n = 8) and chronic (n = 8) mucous membrane pemphigoid and from twelve age-matched healthy individuals. The tissues were embedded in glycol methacrylate and analysed by immunohistochemical methods. Interleukin-2 (IL-2), interferon-γ, transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), tumour necrosis factor-α and proliferating cells (as identified with the antibody Ki-67) were found in both pemphigoid patients and normal controls. Interleukin-4 was not found with this method in either normal or diseased conjunctiva. Significant differences between normal and diseased conjunctiva were found for TGF-β and for proliferating cells, which were both increased in the acute disease group. More intense staining was found in the subacute disease group for IL-2, bFGF and PDGF. Our findings showed that a variety of cytokines were present in normal and diseased bulbar conjunctiva. Acute conjunctival disease in mucous membrane pemphigoid may indicate active scar tissue formation, implied by an increase in TGF-β and the presence of proliferating fibroblasts.

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References

  1. Barbul A, Breslin RJ, Woodyard JP, Wasserkrug HL, Efron G (1989) The effect of in vivo T helper and T suppressor lymphocyte depletion on wound healing. Ann Surg 209:479–483

    PubMed  Google Scholar 

  2. Barbul A, Shawe T, Rotter SM, Efron JE, Wasserkrug HL, Badawy SB (1989) Wound healing in nude mice: a study on the regulatory role of lymphocytes in fibroplasia. Surgery 105:764–769

    PubMed  Google Scholar 

  3. Battagay E, Raines E, Seifert R, Brwen-Pope DF, Ross R (1990) TGF-β induces biomodal proliferation of connective tissue cells via complex control of autocrine PDGF loop. Cell 63:515–563

    PubMed  Google Scholar 

  4. Bernauer W, Wright P, Dart JK, Leonard J, Lightman S (1993) The conjunctiva in acute and chronic mucous membrane pemphigoid. An immunohistochemical analysis. Ophthalmology 100:339–346

    PubMed  Google Scholar 

  5. Bonnefoy JY, Defrance T, Peronne C, Menetrier C, Rousset F, Pène J, De Vries JE, Banchereau J (1988) Human recombinant interleukin 4 induces normal B cells to produce soluble CD 23/IgE-binding factor analogous to that spontaneously released by lymphoblastoid B cell lines. Eur J Immunol 18:117–122

    PubMed  Google Scholar 

  6. Britten K, Howarth PH, Roche WR (1993) Immunohistochemistry on resin sections. A comparison of resin embedding techniques for small mucosal biopsies. Biotech Histochem (in press)

  7. British Bio-technology Limited (1991) Product catalogue. Abingdon, Oxon, UK

    Google Scholar 

  8. Brown DC, Gatter KC (1990) Monoclonal antibody Ki-67: its use in histopathology. Histopathology 17:489–503

    PubMed  Google Scholar 

  9. Campana D, Coustan-Smith E, Janossy G (1989) “Cytoplasmic” expression of nuclear antigens (letter). Leukemia 3:239–240

    PubMed  Google Scholar 

  10. Clark RAF (1991) Cutanous wound repair: a review with emphasis on integrin receptor expression. In: Janssen H, Rooman R, Robertson JIS (eds). Wound healing. Wrightson Biomedical, Petersfield, pp 7–17

    Google Scholar 

  11. DAKO Ltd (1991) Monoclonal antibodies data sheets. High Wycombe, UK

    Google Scholar 

  12. De Juan E, Dickson JS, Hjemeland L (1988) Serum is chemotactic for retinal-derived glial cells. Arch Ophthalmol 16:986–990

    Google Scholar 

  13. De la Maza MS, Tauber J, Foster CS (1988) Cataract surgery in ocular cicatricial pemphigoid. Ophthalmology 96:481–486

    Google Scholar 

  14. Duke-Elder S, MacFaul PA (1965) System of ophthalmology, vol 8. Kimpton, London, pp 496–527

    Google Scholar 

  15. Foster CS (1986) Cicatricial pemphigoid. Trans Am Ophthalmol Soc 84:527–663

    PubMed  Google Scholar 

  16. Foster CS, Rice BA, Dutt JE (1991) Immunopathology of atopic keratoconjunctivitis. Ophthalmology 98:1190–1196

    PubMed  Google Scholar 

  17. Genzyme Corporation (1992) Cytokine research product catalogue. Genzyme Corp., West Malling, Kent, UK

    Google Scholar 

  18. Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13–20

    PubMed  Google Scholar 

  19. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody. J Immunol 133:1710–1715

    PubMed  Google Scholar 

  20. Giacomini P, Tecce R, Gambari R, Sacchi A, Fisher PB, Natali PG (1988) Recombinant IFN-γ, but not IFN-α or IFN-β, enhances MHC- and non-MHC-encoded glycoproteins by protein synthesis-dependent mechanism. J Immunol 140:3073–3081

    PubMed  Google Scholar 

  21. Gordon J, Cairns JA, Millsum MJ, Gills S, Guy GR (1988) Interleukin 4 and soluble CD23 as progression factors for human B lymphocytes: analysis of their interactions with agonists of the phosphoinositide “dual pathway” of signalling. Eur J Immunol 18:1561–1565

    PubMed  Google Scholar 

  22. Grothe C, Unsicker K (1990) Immunohistochemical mapping of basic fibroblast growth factor in the developing and adult rat adrenal gland. Histochemistry 94:141–147

    PubMed  Google Scholar 

  23. Heidenkummer HP, Kampik A, Petrovski B (1992) Proliferative activity in epiretinal membranes. The use of the monoclonal antibody Ki-67 in proliferative vitreoretinal diseases. Retina 12:52–58

    PubMed  Google Scholar 

  24. Hoang-Xuan T, Rodriguez A, Zaltas MM, Rice BA, Foster CS (1990) Ocular rosacea: a histologic and immunopathological study. Opthalmology 97:1468–1475

    Google Scholar 

  25. Kapsenberg ML, Wierenga EA, Bos JD, Jansen HM (1991) Functional subsets of allergen-reactive human CD4+ T cells. Immunol Today 12:392–395

    PubMed  Google Scholar 

  26. Karma A, Tsakinen E, Kainulainen H, Partanen M (1992) Phenotypes of conjunctival inflammartory cells in sarcoidosis. Br J Ophthalmol 76:101–106

    PubMed  Google Scholar 

  27. Kovacs EJ (1991) Fibrogenic cytokines: the role of immune mediators in the development of scar tissue. Immunol Today 12:17–23

    PubMed  Google Scholar 

  28. Kulozik M, Heckmann M, Mauch C, Scharffetter K, Krieg T (1991) Cytokine regulation of collagen metabolism during wound healing in vitro and in vivo. In: Janssen H, Rooman R, Robertson JIS (eds) Wound healing. Wrightson Biomedical, Petersfield, pp 33–39

    Google Scholar 

  29. Lass JH, Thoft RA, Dohlman CH (1983) Idoxuridine-induced conjunctival cicatrization. Arch Ophthalmol 101:747–750

    PubMed  Google Scholar 

  30. Leibovich SJ, Polverini PJ, Shepard HM, Wiseman DM, Shively V, Nuseir N (1987) Macrophage-induced angiogenesis is mediated by tumour necrosis factor-α. Nature 329:630–632

    PubMed  Google Scholar 

  31. Leonard JN, Wright P, Williams DM, Gilkes JJH, Haffenden GP, McMinn RMH, Fry L (1984) The relationship between linear IgA disease and benign mucous membrane pemphigoid. Br J Dermatol 110: 307–314

    PubMed  Google Scholar 

  32. Leonard JN, Hobday CM, Haffenden GP, Griffiths CEM, Powles AV, Wright P, Fry L (1988) Immunofluorescent studies in ocular cicatricial pemphigoid. Br J Dermatol 118:209–217

    PubMed  Google Scholar 

  33. Mondino BJ (1986) Discussion, pp 782–783. In: Pouliquen Y, Patey A, Foster CS, Goichot L, Savodelli M (q.v.)

  34. Mondino BJ (1988) Bullous diseases of the skin and mucous membranes. In: Duane TD, Jaeger EA (eds) Clinical ophthalmology, vol 4. Lippincott, Philadelphia

    Google Scholar 

  35. Mondino BJ, Brown Sl, Lempert S, Jenkins MS (1979) The acute manifestations of cicatricial pemphigoid: diagnosis and treatment. Ophthalmology 86:543–552

    PubMed  Google Scholar 

  36. Mosmann TR, Coffman RL (1989) Heterogeneity of cytokine secretion patterns and functions of helper T cells. Adv Immunol 46:111–147

    PubMed  Google Scholar 

  37. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffmann RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357

    PubMed  Google Scholar 

  38. Narayanan A, Page R (1983) Biosynthesis and regulation of type V collagen in diploid human fibroblasts. J Biol Chem 258:11694–11699

    PubMed  Google Scholar 

  39. Pierce GF, Mustoe TA, Lingelbach J, Masakowski VA, Griffin GL, Senior RM, Deutel TF (1989) Platelet-derived growth factor and transforming growth factor-beta enhance tissue repair activities by unique mechanisms. J Cell Biol 109:429–440

    PubMed  Google Scholar 

  40. Pouliquen Y, Patey A, Foster CS, Goichot L, Savodelli M (1986) Drug-induced cicatricial pemphigoid affecting the conjunctiva. Light and electron microscopic features. Ophthalmology 93:775–783

    PubMed  Google Scholar 

  41. Regan MC, Barbul A (1991) Regulation of wound healing by the T cell-dependent immune system. In: Yanssen H, Rooman R, Robertson JIS (eds) Wound healing. Wrightson Biomedical, Petersfield, pp 21–31

    Google Scholar 

  42. Rice BA, Foster CS (1990) Immunopathology of cicatricial pemphigoid affecting the conjunctiva. Ophthalmology 97:1476–1483

    PubMed  Google Scholar 

  43. Roat MI, Sossi G, Lo CY, Thoft RA (1989) Hyperproliferation of conjunctival fibroblasts from patients with cicatricial pemphigoid. Arch Ophthalmol 107: 1064–1067

    PubMed  Google Scholar 

  44. Sacks EH, Wieczorek R, Jakobiec FA, Knowles DM (1986) Lymphocytic subpopulations in the normal conjunctiva: a monoclonal antibody study. Ophthalmology 93:1276–1283

    PubMed  Google Scholar 

  45. Sacks EH, Jakobiec FA, Wieczorek R, Donnenfeld E, Perry H, Knowles DM (1989) Immunophenotypic analysis of the inflammatory infiltrate in ocular cicatricial pemphigoid. Further evidence for a T cell-mediated disease. Ophthalmology 96:236–243

    PubMed  Google Scholar 

  46. Scott CS, Fey SJ, Larsen PM (1989) Cytoplasmic Ki-67 expression: a reply to Dario Campana, Elaine Cousan-Smith, and George Janossy. Leukemia 3:397

    PubMed  Google Scholar 

  47. Shipley GD, Keeble WW, Hendrickson JE, Coffey RJ Jr, Pittelkow MR (1989) Growth of normal human keratinocytes and fibroblasts in serum-free medium is stimulated by acidic and basic fibroblast growth factor. J Cell Physiol 138: 511–518

    PubMed  Google Scholar 

  48. Skoskiewicz MJ, Colvin RB, Schneeberger EE, Russel PS (1985) Widespread and selective induction of major histocompatibility complex-determined antigens in vivo by γ-interferon. J Exp Med 162:1645–1664

    PubMed  Google Scholar 

  49. Spencer WH (1985)Ophthalmicpathology.Saunders, Philadelphia, pp 14–51

    Google Scholar 

  50. Sporn MB, Roberts AB, Wakefield LM, Crombrugghe B (1987) Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol 105:1039–1045

    PubMed  Google Scholar 

  51. Whitby DJ, Ferguson MJ (1991) Immunohistochemical localization of growth factors in fetal wound healing. Devel Biol 147:207–215

    Google Scholar 

  52. Wiedemann P (1992) Growth factors in retinal diseases: proliferative vitreoretinopathy, proliferative diabetic retinopathy and retinal degeneration. Surv Ophthalmol 36:373–384

    PubMed  Google Scholar 

  53. Wright P (1986) Cicatrizing conjunctivitis. Trans Ophthalmol Soc UK 105:1–17

    PubMed  Google Scholar 

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Authors and Affiliations

  1. University Eye Hospital, Mittlere Strasse 91, CH-4056, Basel, Switzerland

    Wolfgang Bernauer

  2. Moorfields Eye Hospital and Institute of Ophthalmology, London, UK

    Wolfgang Bernauer, Peter Wright, John K. Dart & Susan Lightman

  3. Department of Dermatology, St. Mary's Hospital, London, UK

    Johnatan N. Leonard

Authors
  1. Wolfgang Bernauer
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  2. Peter Wright
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  3. John K. Dart
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  4. Johnatan N. Leonard
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  5. Susan Lightman
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Additional information

This study was supported in part by the Swiss National Science Foundation, the Foundation Florian Verrey, the Swiss Foundation to prevent blindness and by a locally organised research scheme from Moorfields Eye Hospital.

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Bernauer, W., Wright, P., Dart, J.K. et al. Cytokines in the conjunctiva of acute and chronic mucous membrane pemphigoid: An immunohistochemical analysis. Graefe's Arch Clin Exp Ophthalmol 231, 563–570 (1993). https://doi.org/10.1007/BF00936519

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  • DOI: https://doi.org/10.1007/BF00936519

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