The involvement of epithelial Fas in a human model of graft versus host disease.
| Autor: | Ruffin N; IMED AB, 171 65 Solna, Sweden., Ahmed SS, Osorio LM, Wang XN, Jackson GH, Collin MP, Ekre HP, Chiodi F, Dickinson AM |
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| Jazyk: | angličtina |
| Zdroj: | Transplantation [Transplantation] 2011 May 15; Vol. 91 (9), pp. 946-51. |
| DOI: | 10.1097/TP.0b013e318212c833 |
| Abstrakt: | Background: Graft-versus-host disease (GVHD) is an important complication occurring after hematopoietic stem-cell transplantation (HSCT). Animal model studies have shown the involvement of the Fas (APO-1/CD95)/Fas-Ligand pathway in GVHD pathogenesis, but its association with cutaneous GVHD in human remains to be established. Methods: In the present study, Fas involvement in skin damage was assessed using a human skin explant model of GVHD. Fas and FasL expression were measured by immunohistochemistry and blockade of Fas pathway was investigated using an antagonistic anti-human Fas monoclonal antibody. In addition, levels of soluble Fas (sFas) were determined in the serum of patients receiving allogeneic HSCT with and without GVHD. Results: The results showed that Fas up-regulation in the epithelium of human skin explants correlated with graft-versus-host reaction (GVHR) in the skin explant model (P<0.001). Decreased GVHR grades were observed by using a Fas blocking monoclonal antibody. Levels of sFas were increased post-HSCT (P<0.001) but rather than being associated with the severity of GVHD, sFas levels differed with the conditioning treatments the patients received before the HSCT. Conclusions: Higher GVHR grades were associated with increased Fas expression in the epithelium of the skin explants. In addition, by blocking Fas-mediated apoptosis, the GVHR grades were decreased. Our study thus shows the involvement of Fas in cutaneous GVHD damage, and supports the potential use of Fas as a therapeutic target. |
| Databáze: | MEDLINE |
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