Document Detail


Death ligand TRAIL, secreted by CD1a+ and CD14+ cells in blister fluids, is involved in killing keratinocytes in toxic epidermal necrolysis.
MedLine Citation:
PMID:  21255088     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
  Toxic epidermal necrolysis (TEN) is characterized by an acute detachment and destruction of keratinocytes, affecting large areas of the skin. It is often related to adverse drug reactions. Previous studies have shown that effector CD8+ T cells, which accumulate in the blister fluid, are functionally cytotoxic and act through a classical perforin/granzyme B pathway. It has recently been shown that these cytotoxic T cells also secrete granulysin peptide, which is lethal to keratinocytes. These cytotoxic T cells exert their killer activity against autologous keratinocytes in the presence of the drug. However, they are unlikely to be the only effectors of TEN. We therefore searched for soluble death factors in the blister fluids that might kill keratinocytes. We found that the amounts of interferon-γ, TRAIL and TNF-α proteins were significantly greater in TEN blister fluids than in all controls (normal sera, TEN sera, burns and Eosinophilic pustular folliculitis blister fluids) and TNF-like weak inducer of apoptosis (TWEAK) amounts are also greater in all controls except burns. We showed that these proteins acted in synergy to induce the death of keratinocytes in vitro. We also found that TRAIL and TWEAK were secreted by CD1a+ and CD14+ cells present in the blister fluids. Thus, in addition to MHC class I-restricted cytotoxic T lymphocytes (CTLs), which lyse keratinocytes, ligands secreted by non-lymphoid cells capable of inducing keratinocyte death in an MHC class I-independent manner, also seem to be present in the blister fluids of patients with TEN.
Authors:
Elisabeth de Araujo; Valérie Dessirier; Geneviève Laprée; Laurence Valeyrie-Allanore; Nicolas Ortonne; Efstathios N Stathopoulos; Martine Bagot; Armand Bensussan; Maja Mockenhaupt; Jean-Claude Roujeau; Andreas Tsapis
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Publication Detail:
Type:  JOURNAL ARTICLE    
Journal Detail:
Title:  Experimental dermatology     Volume:  20     ISSN:  1600-0625     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-1-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9301549     Medline TA:  Exp Dermatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  107-112     Citation Subset:  -    
Copyright Information:
© 2011 John Wiley & Sons A/S.
Affiliation:
Inserm, U976, Univ Paris-Diderot, Paris, F-75010 France Inserm, U955, Univ Paris 12, Créteil, F-94010 France Dermatology Department, Hôpital Henri Mondor, Créteil, F-94010 France Reference Center on Toxic and Auto-Immune Blistering Diseases, Ile de France, Hôpital Henri Mondor, Créteil, F-94010 France RegiSCAR study group (http://regiscar.uni-freiburg.de/) Department of Pathology, Hôpital Henri Mondor, Créteil, F-94010 France Department of Pathology, University of Crete, School of Medicine, Heraklion, GR-71003 Greece Dermatology Department, Hôpital Saint Louis, Paris, F-75010 France Dokumentationszentrum schwerer Hautreaktionen (dZh), University Medical Center, Freiburg, D-79104 Germany.
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