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

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.

Regression of basal cell carcinoma by intralesional interferon-alpha treatment is mediated by CD95 (Apo-1/Fas)-CD95 ligand-induced suicide.

“…In this study, we found that the BCCs of untreated patients were strongly CD95L-positive. CD95 was not detectable, confirming the results of other groups (30,31). Thus, BCC formation in untreated patients may be due to the ability of the tumor cells to lyse attacking CD95-expressing effector T cells via their CD95L.…”

Laser capture microdissection-based in vivo genomic profiling of wound keratinocytes identifies similarities and differences to squamous cell carcinoma

“…The endogenous expression of galectin 7 in keratinocytes and the specific upregulation of galectin 7 expression in wound edge keratinocytes during reepithelialization identified here strongly implicate galectin 7 as critical to wound reepithelialization. The Fas I receptor has an essential role in regulating apoptosis of keratinocytes in response to genotoxic stress, and the receptor is expressed in both basal and suprabasal keratinocytes of the normal epidermis (Oishi et al, 1994;Lee et al, 1998;Wehrli et al, 2000). The specific downregulation of the Fas I receptor in wound edge keratinocytes identified here may be critically related to wound reepithelialization by desensitizing wound keratinocytes to the many apoptosis-inducing stimuli that are associated with wounding.…”

Cytokine Gene Expression During the Development of Graft Coronary Artery Disease in Mice

“…22 Fas ligand is inducibly expressed on the cell surface of CTL and transmit death signals into Fas-expressing target cells. 23 Fas can be expressed constitutively or inducibly by a variety of cells, including vascular endothelial cells 24,25 and cardiomyocytes. 26 Another possible role of the Fas-Fas ligand in allograft rejection is to regulate mechanisms that limit the associated inflammation.…”