Research Article | Open Access
Expression of Selected Integrins and Selectins in Bullous Pemphigoid
Blister development in bullous pemphigoid (BP) results from destruction of hemidesmosomes and basement membrane components within the dermoepidermal junction by autoantibodies. Adhesion molecules can take part in pathogenesis of this disease. The aim of the study was to determine the localization and expression of L- and E-selectins and 1, 3, and 4 integrins by immunohistochemistry in skin lesions of 21 patients with BP, compared with 10 healthy subjects. Expression of L and E selectins and 1, 3 integrins was detected mainly in basal keratinocytes and in inflammatory infiltrates in the dermis, expression of 4 integrin was irregular and was detected mainly in dermal part of the blister, while in the control group only weak and single expression of the examined molecules was detected in basal keratinocytes and endothelium cells. The obtained results reveal the important role of selected selectins and integrins in development of skin lesions in BP.
- J. R. Stanley, “Cell adhesion molecules as targets of autoantibodies in pemphigus and pemphigoid, bullous diseases due to defective epidermal cell adhesion,” Advances in Immunology, vol. 53, pp. 291–325, 1993.
- E. Schmidt, K. Obe, E.-B. Bröcker;, and D. Zillikens, “Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid,” Archives of Dermatology, vol. 136, no. 2, pp. 174–178, 2000.
- R. E. Jordon, E. H. Beutner, E. Witebsky, G. Blumental, W. L. Hale, and W. F. Lever, “Basement zone antibodies in bullous pemphigoid,” Journal of the American Medical Association, vol. 200, no. 9, pp. 751–756, 1967.
- E. Schmidt, S. Reimer, N. Kruse et al., “Autoantibodies to BP180 associated with bullous pemphigoid release interleukin-6 and interleukin-8 from cultured human keratinocytes,” Journal of Investigative Dermatology, vol. 115, no. 5, pp. 842–848, 2000.
- S. A. Grando, B. T. Glukhenky, G. N. Drannik, E. V. Epshtein, A. P. Kostromin, and T. A. Korostash, “Mediators of inflammation in blister fluids from patients with pemphigus vulgaris and bullous pemphigoid,” Archives of Dermatology, vol. 125, no. 7, pp. 925–930, 1989.
- M. Ståhle-Bäckdahl, M. Inoue, G. J. Giudice, and W. C. Parks, “92-kD gelatinase is produced by eosinophils at the site of blister formation in bullous pemphigoid and cleaves the extracellular domain of recombinant 180-kD bullous pemphigoid autoantigen,” Journal of Clinical Investigation, vol. 93, no. 5, pp. 2022–2030, 1994.
- A. J. Freemont, “Demystified ... adhesion molecules,” Journal of Clinical Pathology—Molecular Pathology, vol. 51, no. 4, pp. 175–184, 1998.
- M. Graeber, B. S. Baker, J. J. Garioch, H. Valdimarsson, J. N. Leonard, and L. Fry, “The role of cytokines in the generation of skin lesions in dermatitis herpetiformis,” British Journal of Dermatology, vol. 129, no. 5, pp. 530–532, 1993.
- Z. Liu, M. Zhao, N. Li, L. A. Diaz, and T. N. Mayadas, “Differential roles for integrins in experimental autoimmune bullous pemphigoid,” Blood, vol. 107, no. 3, pp. 1063–1069, 2006.
- U. H. von Andrian and B. Engelhardt, “ integrins as therapeutic targets in autoimmune disease,” New England Journal of Medicine, vol. 348, no. 1, pp. 68–72, 2003.
- A. Moreno, C. Lucena, A. López, J. J. Garrido, L. L. de Pérez, and D. Llanes, “Immunohistochemical analysis of integrin (CD61): expression in pig tissues and human tumors,” Histology and Histopathology, vol. 17, no. 2, pp. 347–352, 2002.
- A. E. Berman, N. I. Kozlova, and G. E. Morozevich, “Integrins: structure and signaling,” Biochemistry (Moscow), vol. 68, no. 12, pp. 1284–1299, 2003.
- J.-P. Xiong, T. Stehle, S. L. Goodman, and M. A. Arnaout, “New insights into the structural basis of integrin activation,” Blood, vol. 102, no. 4, pp. 1155–1159, 2003.
- R. O. Hynes, “Integrins: versatility, modulation, and signaling in cell adhesion,” Cell, vol. 69, no. 1, pp. 11–25, 1992.
- M. H. Ginsberg, X. Du, and E. F. Plow, “Inside-out integrin signalling,” Current Opinion in Cell Biology, vol. 4, no. 5, pp. 766–771, 1992.
- T. E. O'Toole, Y. Katagiri, R. J. Faull et al., “Integrin cytoplasmic domains mediate inside-out signal transduction,” Journal of Cell Biology, vol. 124, no. 6, pp. 1047–1059, 1994.
- R. O. Hynes, “Integrins: bidirectional, allosteric signaling machines,” Cell, vol. 110, no. 6, pp. 673–687, 2002.
- T. A. Springer, “Adhesion receptors of the immune system,” Nature, vol. 346, no. 6283, pp. 425–434, 1990.
- D. Bouvard, C. Brakebusch, E. Gustafsson et al., “Functional consequences of integrin gene mutations in mice,” Circulation Research, vol. 89, no. 3, pp. 211–223, 2001.
- M. A. Stepp, S. Spurr-Michaud, A. Tisdale, J. Elwell, and I. K. Gipson, “ integrin heterodimer is a component of hemidesmosomes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 22, pp. 8970–8974, 1990.
- J. Koster, D. Geerts, B. Favre, L. Borradori, and A. Sonnenberg, “Analysis of the interactions between BP180, BP230, plectin and the integrin important for hemidesmosome assembly,” Journal of Cell Science, vol. 116, no. 2, pp. 387–399, 2003.
- X.-Y. Liu, S. Timmons, Y.-Z. Lin, and J. Hawiger, “Identification of a functionally important sequence in the cytoplasmic tail of integrin by using cell-permeable peptide analogs,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 21, pp. 11819–11824, 1996.
- R. A. J. Eady, “The hemidesmosome: a target in auto-immune bullous disease,” Dermatology, vol. 189, supplement 1, pp. 38–41, 1994.
- L. Borradori, P. J. Koch, C. M. Niessen, S. Erkeland, M. R. Van Leusden, and A. Sonnenberg, “The localization of bullous pemphigoid antigen 180 (BP180) in hemidesmosomes is mediated by its cytoplasmic domain and seems to be regulated by the integrin subunit,” Journal of Cell Biology, vol. 136, no. 6, pp. 1333–1347, 1997.
- S. B. Hopkinson, K. Findlay, G. W. deHart, and J. C. R. Jones, “Interaction of BP180 (type XVII collagen) and integrin is necessary for stabilization of hemidesmosome structure,” Journal of Investigative Dermatology, vol. 111, no. 6, pp. 1015–1022, 1998.
- S. Kumari, K. C. Bhol, R. K. Simmons et al., “Identification of ocular cicatricial pemphigoid antibody binding site(s) in human integrin,” Investigative Ophthalmology and Visual Science, vol. 42, no. 2, pp. 379–385, 2001.
- M. Leverkus, K. Bhol, Y. Hirako et al., “Cicatricial pemphigoid with circulating autoantibodies to integrin, bullous pemphigoid 180 and bullous pemphigoid 230,” British Journal of Dermatology, vol. 145, no. 6, pp. 998–1004, 2001.
- R. Y. Chan, K. Bhol, N. Tesavibul et al., “The role of antibody to human integrin in conjunctival basement membrane separation: possible in vitro model for ocular cicatricial pemphigoid,” Investigative Ophthalmology and Visual Science, vol. 40, no. 10, pp. 2283–2290, 1999.
- S. Tyagi, K. Bhol, K. Natarajan, C. Livir-Rallatos, C. S. Foster, and A. R. Ahmed, “Ocular cicatricial pemphigoid antigen: partial sequence and biochemical characterization,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 25, pp. 14714–14719, 1996.
- K. C. Bhol, L. Goss, S. Kumari, J. E. Colon, and A. R. Ahmed, “Autoantibodies to human integrin in patients with oral pemphigoid,” Journal of Dental Research, vol. 80, no. 8, pp. 1711–1715, 2001.
- K. C. Bhol, M. J. Dans, R. K. Simmons, C. S. Foster, F. G. Giancotti, and A. R. Ahmed, “The autoantibodies to integrin of patients affected by ocular cicatricial pemphigoid recognize predominantly epitopes within the large cytoplasmic domain of human ,” Journal of Immunology, vol. 165, no. 5, pp. 2824–2829, 2000.
- K. A. Rashid, J. N. H. Stern, and A. R. Ahmed, “Identification of an epitope within human integrin subunit for the binding of autoantibody and its role in basement membrane separation in oral pemphigoid,” Journal of Immunology, vol. 176, no. 3, pp. 1968–1977, 2006.
- M. A. Kurpakus, V. Quaranta, and J. C. R. Jones, “Surface relocation of integrins and assembly of hemidesmosomes in an in vitro model of wound healing,” Journal of Cell Biology, vol. 115, no. 6, pp. 1737–1750, 1991.
- L. D'Auria, P. Cordiali Fei, M. Pietravalle et al., “The serum levels of sE-selectin are increased in patients with bullous pemphigoid or pemphigus vulgaris. Correlation with the number of skin lesions and recovery after corsticosteroid therapy,” British Journal of Dermatology, vol. 137, no. 1, pp. 59–64, 1997.
- W. E. Parish, “Inflammation,” in Rook, Wilkinson, Ebling Textbook of Dermatology, R. H. Champion, J. L. Burton, D. A. Burner, and S. M. Breathnach, Eds., pp. 229–276, Blackwell Science, Oxford, UK, 6th edition, 1998.
- S. Ghosh, E. Goldin, F. H. Gordon et al., “Natalizumab for active Crohn's disease,” New England Journal of Medicine, vol. 348, no. 1, pp. 24–32, 2003.
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