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. 1991 Apr;84(1):157–162. doi: 10.1111/j.1365-2249.1991.tb08140.x

Adhesion molecule expression in psoriatic skin lesions and the influence of cyclosporin A.

C Horrocks 1, J I Duncan 1, A M Oliver 1, A W Thomson 1
PMCID: PMC1535371  PMID: 2015706

Abstract

Normal skin of healthy individuals and both lesional and uninvolved skin from patients with psoriasis before and after receiving cyclosporin A (CsA; 2.5 or 5 mg/kg per day) was examined by immunocytochemistry for differences in expression of adhesion-relevant epitopes. Normal, lesional and uninvolved skin all showed staining of basal keratinocytes for CD29 (the common beta chain of the beta 1-integrin family). No other adhesion molecule investigated was detected on structural components of normal skin. In uninvolved skin, weak expression of CD54 (intercellular adhesion molecule 1, ICAM-1) was noted on vascular endothelium. Uninvolved keratinocytes were found to stain with anti-CD58 (leucocyte function-associated antigen 3, LFA-3) and there was weak expression of CD11b (alpha chain of complement C3bi receptor) and CD11c (alpha chain of p150, 95 molecule) but not CD11a (leucocyte function-associated antigen 1, LFA-1, alpha chain) on those cells. In lesional skin, in addition to expression of CD58, there was also enhanced expression of CD11c. Weak expression of CD54 on keratinocytes was also observed. Lesional blood vessels were found to stain strongly with anti-CD54, CD29 and CD58. CD11a was expressed only on infiltrating mononuclear cells. CsA treatment produced marked clinical improvement, accompanied by the loss of CD54 expression on keratinocytes. However, despite the loss of T cells from lesional skin with CsA treatment, CD54 persisted on blood vessels. CsA was found to have no effect on keratinocyte expression of CD29, CD58 or CD11b and c. The persistence of CD54 on vascular endothelium and of adhesion molecule expression on keratinocytes, despite resolution of the skin lesions, may explain the universal and rapid recurrence of psoriasis on cessation of CsA administration.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Auböck J., Romani N., Grubauer G., Fritsch P. HLA-DR expression on keratinocytes is a common feature of diseased skin. Br J Dermatol. 1986 Apr;114(4):465–472. doi: 10.1111/j.1365-2133.1986.tb02851.x. [DOI] [PubMed] [Google Scholar]
  2. Baker B. S., Powles A. V., Valdimarsson H., Fry L. An altered response by psoriatic keratinocytes to gamma interferon. Scand J Immunol. 1988 Dec;28(6):735–740. doi: 10.1111/j.1365-3083.1988.tb01507.x. [DOI] [PubMed] [Google Scholar]
  3. Baker B. S., Swain A. F., Fry L., Valdimarsson H. Epidermal T lymphocytes and HLA-DR expression in psoriasis. Br J Dermatol. 1984 May;110(5):555–564. doi: 10.1111/j.1365-2133.1984.tb04678.x. [DOI] [PubMed] [Google Scholar]
  4. Barker J. N., Navsaria H. A., Leigh I. M., MacDonald D. M. Gamma-interferon induced human keratinocyte HLA-DR synthesis: the role of dermal activated T lymphocytes. Br J Dermatol. 1988 Nov;119(5):567–572. doi: 10.1111/j.1365-2133.1988.tb03466.x. [DOI] [PubMed] [Google Scholar]
  5. Bjerke J. R., Livden J. K., Degré M., Matre R. Interferon in suction blister fluid from psoriatic lesions. Br J Dermatol. 1983 Mar;108(3):295–299. doi: 10.1111/j.1365-2133.1983.tb03967.x. [DOI] [PubMed] [Google Scholar]
  6. Dustin M. L., Singer K. H., Tuck D. T., Springer T. A. Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule 1 (ICAM-1). J Exp Med. 1988 Apr 1;167(4):1323–1340. doi: 10.1084/jem.167.4.1323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ellis C. N., Gorsulowsky D. C., Hamilton T. A., Billings J. K., Brown M. D., Headington J. T., Cooper K. D., Baadsgaard O., Duell E. A., Annesley T. M. Cyclosporine improves psoriasis in a double-blind study. JAMA. 1986 Dec 12;256(22):3110–3116. [PubMed] [Google Scholar]
  8. Farber E. M., Nickoloff B. J., Recht B., Fraki J. E. Stress, symmetry, and psoriasis: possible role of neuropeptides. J Am Acad Dermatol. 1986 Feb;14(2 Pt 1):305–311. doi: 10.1016/s0190-9622(86)70034-0. [DOI] [PubMed] [Google Scholar]
  9. Fradin M. S., Ellis C. N., Voorhees J. J. Efficacy of cyclosporin A in psoriasis: a summary of the United States' experience. Br J Dermatol. 1990 Jun;122 (Suppl 36):21–25. doi: 10.1111/j.1365-2133.1990.tb02878.x. [DOI] [PubMed] [Google Scholar]
  10. Granelli-Piperno A. Lymphokine gene expression in vivo is inhibited by cyclosporin A. J Exp Med. 1990 Feb 1;171(2):533–544. doi: 10.1084/jem.171.2.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Griffiths C. E., Nickoloff B. J. Keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression precedes dermal T lymphocytic infiltration in allergic contact dermatitis (Rhus dermatitis). Am J Pathol. 1989 Dec;135(6):1045–1053. [PMC free article] [PubMed] [Google Scholar]
  12. Griffiths C. E., Powles A. V., Leonard J. N., Fry L., Baker B. S., Valdimarsson H. Clearance of psoriasis with low dose cyclosporin. Br Med J (Clin Res Ed) 1986 Sep 20;293(6549):731–732. doi: 10.1136/bmj.293.6549.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Griffiths C. E., Voorhees J. J., Nickoloff B. J. Characterization of intercellular adhesion molecule-1 and HLA-DR expression in normal and inflamed skin: modulation by recombinant gamma interferon and tumor necrosis factor. J Am Acad Dermatol. 1989 Apr;20(4):617–629. doi: 10.1016/s0190-9622(89)70073-6. [DOI] [PubMed] [Google Scholar]
  14. Hogg N. The leukocyte integrins. Immunol Today. 1989 Apr;10(4):111–114. doi: 10.1016/0167-5699(89)90238-7. [DOI] [PubMed] [Google Scholar]
  15. Horrocks C., Duncan J. I., Sewell H. F., Ormerod A. D., Thomson A. W. Differential effects of cyclosporine A on Langerhans cells and regulatory T-cell populations in severe psoriasis: an immunohistochemical and flow cytometric analysis. J Autoimmun. 1990 Oct;3(5):559–570. doi: 10.1016/s0896-8411(05)80021-6. [DOI] [PubMed] [Google Scholar]
  16. Keizer G. D., Te Velde A. A., Schwarting R., Figdor C. G., De Vries J. E. Role of p150,95 in adhesion, migration, chemotaxis and phagocytosis of human monocytes. Eur J Immunol. 1987 Sep;17(9):1317–1322. doi: 10.1002/eji.1830170915. [DOI] [PubMed] [Google Scholar]
  17. Kupper T. S. Mechanisms of cutaneous inflammation. Interactions between epidermal cytokines, adhesion molecules, and leukocytes. Arch Dermatol. 1989 Oct;125(10):1406–1412. doi: 10.1001/archderm.125.10.1406. [DOI] [PubMed] [Google Scholar]
  18. Lewis R. E., Buchsbaum M., Whitaker D., Murphy G. F. Intercellular adhesion molecule expression in the evolving human cutaneous delayed hypersensitivity reaction. J Invest Dermatol. 1989 Nov;93(5):672–677. doi: 10.1111/1523-1747.ep12319838. [DOI] [PubMed] [Google Scholar]
  19. Makgoba M. W., Sanders M. E., Shaw S. The CD2-LFA-3 and LFA-1-ICAM pathways: relevance to T-cell recognition. Immunol Today. 1989 Dec;10(12):417–422. doi: 10.1016/0167-5699(89)90039-X. [DOI] [PubMed] [Google Scholar]
  20. Mozzanica N., Cattaneo A., Pigatto P. D., Finzi A. F. Cyclosporine A in psoriasis: an immunohistological study. Transplant Proc. 1988 Jun;20(3 Suppl 4):78–84. [PubMed] [Google Scholar]
  21. Nickoloff B. J., Fisher G. J., Mitra R. S., Voorhees J. J. Additive and synergistic antiproliferative effects of cyclosporin A and gamma interferon on cultured human keratinocytes. Am J Pathol. 1988 Apr;131(1):12–18. [PMC free article] [PubMed] [Google Scholar]
  22. Nickoloff B. J. Role of interferon-gamma in cutaneous trafficking of lymphocytes with emphasis on molecular and cellular adhesion events. Arch Dermatol. 1988 Dec;124(12):1835–1843. [PubMed] [Google Scholar]
  23. Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
  24. Powles A. V., Baker B. S., Valdimarsson H., Hulme B., Fry L. Four years of experience with cyclosporin A for psoriasis. Br J Dermatol. 1990 Jun;122 (Suppl 36):13–19. doi: 10.1111/j.1365-2133.1990.tb02877.x. [DOI] [PubMed] [Google Scholar]
  25. Smolle J. HLA-DR-antigen bearing keratinocytes in various dermatologic disorders. Acta Derm Venereol. 1985;65(1):9–13. [PubMed] [Google Scholar]
  26. Staquet M. J., Dezutter-Dambuyant C., Zambruno G., Schmitt D. Human epidermal basal keratinocytes express CDw29 antigens. Br J Dermatol. 1989 Nov;121(5):577–585. doi: 10.1111/j.1365-2133.1989.tb08189.x. [DOI] [PubMed] [Google Scholar]
  27. Terui T., Aiba S., Kato T., Tanaka T., Tagami H. HLA-DR antigen expression on keratinocytes in highly inflamed parts of psoriatic lesions. Br J Dermatol. 1987 Jan;116(1):87–93. doi: 10.1111/j.1365-2133.1987.tb05794.x. [DOI] [PubMed] [Google Scholar]
  28. Voorhees J. J. Leukotrienes and other lipoxygenase products in the pathogenesis and therapy of psoriasis and other dermatoses. Arch Dermatol. 1983 Jul;119(7):541–547. [PubMed] [Google Scholar]

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