Internalization of constitutive desmogleins with the subsequent induction of desmoglein 2 in pemphigus lesions.
Acantholytic blisters in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are caused by a dissociation of desmosomes mediated by autoantibodies against desmoglein (Dsg) 3 and Dsg 1, respectively. The blistering occurs at the suprabasilar level in PV and at the subcorneal level in PF, which corresponds to the distribution of target antigens in the epidermis: there is a more prominent expression of Dsg 1 in the upper layer, whereas Dsg 3 is more prominent in the lower layer. To elucidate the histogenesis of acantholysis, we studied the alterations of the desmosomal components and the expression pattern of Dsg isoforms in the lesional and perilesional epidermis of pemphigus patients. The results demonstrated an internalization of the desmosomes in the lower epidermis of PV, PF and pemphigus vegetans. A similar phenomenon was induced in monolayers of keratinocytes cultured with PV sera. However, little change was observed in E-cadherin expression until acantholysis became manifest. This internalization occurred prior to overt acantholysis, and was frequently associated with the induction of Dsg 2 expression in the basilar or lower layers of the epidermis. These findings indicate an alteration of Dsg isoform expression in subclinical pemphigus lesions, which might be related to the characteristic acantholytic patterns: the suprabasilar layer in PV and the upper epidermis in PF.
Iwatsuki
K
K
Department of Dermatology, Fukushima Medical University School of Medicine, 1-Hikarigaoka, Fukushima 960-1295, Japan. keijiiwa@cc.fmu.ac.jp
Han
G W
GW
Fukuti
R
R
Ohtsuka
M
M
Kikuchi
S
S
Akiba
H
H
Kaneko
F
F
D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism; D051301:Desmoglein 2; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D015603:Keratinocytes / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D010392:Pemphigus / Q000378:metabolism*
D003598:Cytoskeletal Proteins; C495314:DSG2 protein, human; D051301:Desmoglein 2; D051182:Desmogleins; D051180:Desmoplakins