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The Fas pathway mediates the acantholytic process of Pemphigus
Author(s) -
AvalosDíaz Esperanza,
PachecoTovar MaríaGuadalupe,
VegaMemije Elisa,
BollainyGoytia JuanJosé,
LópezRobles Eréndira,
HojyoTomoka MariaTeresa,
DomínguezSoto Luciano,
HerreraEsparza Rafael
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a771-c
Subject(s) - acantholysis , pemphigus , fas ligand , apoptosis , desmoglein 1 , cd8 , autoantibody , pathology , antibody , biology , medicine , programmed cell death , immunology , antigen , biochemistry
Pemphigus is an autoimmune disease, characterized by intraepidermal blisters triggered by autoantibodies against desmoglein 1 and 3 proteins. Pemphigus autoantibodies induce epithelial cell detachment or acantholysis, apparently mediated by a kinase down signal transduction that participates in the desmosomal breaking down. Acantholysis is enhanced by the local production of TNF, which produce apoptosis. Present work addresses the issue of apoptosis in the blister formation of pemphigus. Twenty biopsies of Pemphigus patients were studied by H‐E staining; apoptosis was defined by TUNEL, and the expression of Fas, FasL and Caspase 3 and Bax was studied by in situ hybridization and immunohistochemistry. Cell infiltrates were studied by immunofluroescence with monoclonal anti‐CD3, CD4, CD8 and CD19 antibodies. All the biopsies showed intraepidermal blisters, acantholytic cells and inflammatory infiltrates. Fas, FasL, Bax and Caspase 3 mRNAs and proteins, were detected in the blisters. Cell infiltrates were composed by CD3 (78%) mainly of the CD8 subset, and B lymphocytes (22%) located in basal area of the blister. Interestingly, the acantholytic cells and keratinocytes around the blister over‐expressed Fas and exhibited apoptotic features; meanwhile CD8 cells over‐expressed the FasL. In conclusion, apoptosis is linked to acantholysis. The presence of pemphigus antibody and CD8 cells in the blister suggest that they feed the Fas pathway that results in acantholysis.