Document Detail


The Involvement of Epithelial Fas in a Human Model of Graft Versus Host Disease.
MedLine Citation:
PMID:  21403589     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Nicolas Ruffin; Shaheda S Ahmed; Lyda M Osorio; Xiao Nong Wang; Graham H Jackson; Matthew P Collin; Hans-Peter Ekre; Francesca Chiodi; Anne M Dickinson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-11
Journal Detail:
Title:  Transplantation     Volume:  -     ISSN:  1534-6080     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 IMED AB, 171 65 Solna, Sweden. 2 Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom. 3 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
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