Skip to main content
SpringerLink
Log in

Distribution of apoptosis-mediating Fas antigen in human skin and effects of anti-Fas monoclonal antibody on human epidermal keratinocyte and squamous cell carcinoma cell lines

  • Original Contributions
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Fast antigen is a cell surface protein that mediates apoptosis. Using immunohistological, flow cytometry and electron microscopic analyses, we investigated the expression of Fas antigen on various skin tissues, and on cultured SV40-transformed human epidermal keratinocyte cell line KJD and human skin squamous cell carcinoma cell line HSC. The Fas antigen was widely distributed in skin components such as the keratinocytes in the lower portion of the epidermis, epidermal dendritic cells, endothelial cells, fibroblasts, apocrine glands, eccrine sweat glands, sebaceous glands, some normal melanocytes and infiltrating lymphoid cells. It was also strongly expressed on the keratinocytes of lichenoid eruptions seen in lupus erythematosus and lichen planus, and on the spongiotic or acanthotic epidermis seen in chronic eczema, adult T-cell leukaemia/lymphoma (ATLL) and atopic dermatitis. Its expression was closely correlated with lymphoid infiltrating cells and it was strongly expressed in lymphoid neoplastic cells, particularly ATLL cells, and fibroblasts seen in dermatofibroma. However, the antigen was not detected on basal cell epithelioma cells, some malignant melanomas or any junctional naevi. The cell lines KJD and HSC strongly expressed the Fas antigen, and crosslinking of the Fas antigen by an anti-Fas monoclonal antibody induced apoptosis of these cell lines. These results indicate that the apoptosis-mediating Fas antigen may play an important role in normal skin turnover and cell differentiation, in immune regulation of skin tumours, and in the pathogenesis of various skin diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Akosa AB, Lampert IA (1991) The sweat gland in cutaneous vasculitis. Histopathology 18: 553–558

    Google Scholar 

  2. Akosa AB, Lampert IA (1991) Sweat gland abnormalities in lichenoid dermatosis. Histopathology 19: 345–349

    Google Scholar 

  3. Cohen JJ, Duke RC (1984) Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. J Immunol 132: 38–42

    Google Scholar 

  4. Curson C, Weedon D (1979) Spontaneous regression in basal cell carcinomas. J Cutan Pathol 6: 432–437

    Google Scholar 

  5. Dealtry GB, Naylor MS, Fiers W, Balkwill FR (1987) DNA fragmentation and cytotoxicity caused by tumor necrosis factor is enhanced by interferon-γ. Eur J Immunol 17: 689–693

    Google Scholar 

  6. Duke RC, Cohen JJ, Chervenak R (1986) Differences in target cell DNA fragmentation induced by mouse cytotoxic T lymphocytes and natural killer cells. J Immunol 137: 1442–1447

    Google Scholar 

  7. Gavrieli Y, Sherman Y, Ben-Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119: 493–501

    Google Scholar 

  8. Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y, Nagata S (1991) The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66: 233–243

    Google Scholar 

  9. Jenkinson EJ, Kingston R, Smith CA, Williams GT, Owen JJT (1989) Antigen-induced apoptosis in developing T cells: a mechanism for negative selection of the T cell receptor repertoire. Eur J Immunol 19: 2175–2177

    Google Scholar 

  10. Johnson D, Lanahan A, Buck CR, Sehgal A, Morgan C, Mercer E, Bothwell M, Chao M (1986) Expression and structure of the human NGF receptor. Cell 47: 545–554

    Google Scholar 

  11. Kerr JFR, Searle J (1972) A suggested explanation for the paradoxically slow growth rate of basal-cell carcinomas that contain numerous mitotic figures. J Pathol 107: 41–44

    Google Scholar 

  12. Kobayashi N, Hamamoto Y, Yamamoto N, Ishii A, Yonehara M, Yonehara S (1990) Anti-Fas monoclonal antibody is cytocidal to human immunodeficiency virus-infected cells without augmenting viral replication. Proc Natl Acad Sci USA 87: 9620–9624

    Google Scholar 

  13. Le J, Prensky W, Henriksen D, Vilcek J (1982) Synthesis of alpha and gamma interferons by a human cutaneous lymphoma with helper T-cell phenotype. Cell Immunol 72: 157–165

    Google Scholar 

  14. Loetscher H, Pan Y-CE, Lahm H-W, Gentz R, Brockhaus M, Tabuchi H, Lesslauer W (1990) Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell 61: 351–359

    Google Scholar 

  15. Maeyer-Guignard J, Maeyer E (1985) Interferon. In: Gresser I (ed) Immunomodulation by interferons: recent developments, vol 6. Academic Press, London, pp 69–91

    Google Scholar 

  16. Matsuda M, Matsutani H, Nakamura H, Miyajima S, Yamauchi A, Yonehara S, Uchida A, Irimajiri K, Horiuchi A, Yodoi J (1991) Protective activity of adult T cell leukemia-derived factor (ADF) against tumor necrosis factor-dependent cytotoxicity on U937 cells. J Immunol 147: 3837–3841

    Google Scholar 

  17. Nakasone T, Araki K, Masuda M, Oshiro K, Arakaki H, Shimoji T, Shinzato O, Mimura G (1992) Immune responses and serum levels of cytokines in adult T-cell leukemia patients and human T-cell leukemia virus type-I carriers. Eur J Haematol 48: 99–104

    Google Scholar 

  18. Rubin BY, Smith LJ, Hellermann GR, Lunn RM, Richardson NK, Anderson SL (1988) Correlation between the anticellular and DNA fragmenting activities of tumor necrosis factor. Cancer Res 48: 6006–6010

    Google Scholar 

  19. Salahuddin SZ, Markham PD, Lindner SG, Gootenberg J, Popovic M, Hemmi H, Sarin PS, Gallo RC (1984) Lymphokine production by cultured human T cells transformed by human T-cell leukemia-lymphoma virus-I. Science 223: 703–707

    Google Scholar 

  20. Schall TJ, Lewis M, Koller KJ, Lee A, Rice GC, Wong GHW, Gatanaga T, Granger GA, Lentz R, Raab H, Kohr WJ, Goeddel DV (1990) Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell 61: 361–370

    Google Scholar 

  21. Schmid DS, Tite JP, Ruddle NH (1986) DNA fragmentation: manifestation of target cell destruction mediated by cytotoxic T-cell lines, lymphotoxin-secreting helper T-cell clones, and cell-free lymphotoxin-containing supernatant. Proc Natl Acad Sci USA 83: 1881–1885

    Google Scholar 

  22. Sellins KS, Cohen JJ (1987) Gene induction by γ-irradiation leads to DNA fragmentation in lymphocytes. J Immunol 139: 3199–3206

    Google Scholar 

  23. Smith CA, Williams GT, Kingston R, Jenkinson EJ, Owen JJT (1989) Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures. Nature 337: 181–184

    Google Scholar 

  24. Smith CA, Davis T, Anderson D, Solam L, Beckmann MP, Jerzy R, Dower SK, Cosman D, Goodwin RG (1990) A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science 248: 1019–1023

    Google Scholar 

  25. Stamenkovic I, Clark EA, Seed B (1989) A B-lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas. EMBO J 8: 1403–1410

    Google Scholar 

  26. Takahashi S, Maecker HT, Levy R (1989) DNA fragmentation and cell death mediated by T cell antigen receptor/CD3 complex on a leukemia T cell line. Eur J Immunol 19: 1911–1919

    Google Scholar 

  27. Uehara T, Miyawaki T, Ohta K, Tamaru Y, Yokoi T, Nakamura S, Taniguchi N (1992) Apoptotic cell death of primed CD45RO+ T lymphocytes in Epstein-Barr virus-induced infectious mononucleosis. Blood 80: 452–458

    Google Scholar 

  28. Walker NI, Harmon BV, Gobe GC, Kerr JFR (1988) Patterns of cell death. Methods Achievements Exp Pathol 13: 18–54

    Google Scholar 

  29. Watanabe-Fukunaga R, Brannan CI, Itoh N, Yonehara S, Copeland NG, Jenkins NA, Nagata S (1992) The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J Immunol 148: 1274–1279

    Google Scholar 

  30. Weedon D (1990) Apoptosis. Adv Dermatol 5: 243–256

    Google Scholar 

  31. Wyllie AH, Kerr JFR, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68: 251–306

    Google Scholar 

  32. Yonehara S, Ishii A, Yonehara M (1989) A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-down-regulated with the receptor of tumor necrosis factor. J Exp Med 169: 1747–1756

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, School of Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, Japan

    M. Oishi, K. Maeda & S. Sugiyama

Authors
  1. M. Oishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Sugiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oishi, M., Maeda, K. & Sugiyama, S. Distribution of apoptosis-mediating Fas antigen in human skin and effects of anti-Fas monoclonal antibody on human epidermal keratinocyte and squamous cell carcinoma cell lines. Arch Dermatol Res 286, 396–407 (1994). https://doi.org/10.1007/BF00371800

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00371800

Key words

Search

Navigation