Apoptosis in pemphigus.
Pemphigus is a severe autoimmune blistering skin disease. The two main forms of pemphigus, pemphigus vulgaris and pemphigus foliaceus, are primarily caused by autoantibodies against the desmosomal cadherins desmoglein 1 and desmoglein 3. The histopathological hallmark is the loss of cell adhesion between neighbouring keratinocytes, a phenomenon called acantholysis. Various underlying mechanisms of acantholysis have been described including apoptosis. The role of apoptosis in pemphigus pathogenesis is unclear at present and the focus of this review. While characteristic signs of apoptosis can be found in lesional patient skin these can be missing in very early lesions of macroscopically perilesional skin where acantholysis is detected by light microscopy. Under experimental conditions, activation of apoptotic signalling can be induced by pemphigus IgG as well as by pemphigus serum which contains large amounts of Fas ligand. Studies using caspase inhibitors which were effective to block acantholysis indicate that the apoptotic machinery contributes to cell dissociation. However, acantholysis can occur in the absence of apoptosis which demonstrates that apoptosis is not strictly required for skin blistering in pemphigus. Taken together, signalling events leading to apoptosis including activation of executioner caspases are not required but may participate in the cellular response to pemphigus autoantibodies leading to acantholysis.
Schmidt
Enno
E
Department of Dermatology, University of Lübeck, Lübeck, Germany. enno.schmidt@uk-sh.de
Waschke
Jens
J
D000051:Acantholysis / Q000276:immunology / Q000473:pathology; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D020169:Caspases / Q000378:metabolism; D053222:Fas Ligand Protein / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D010392:Pemphigus / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction
D001323:Autoantibodies; D053222:Fas Ligand Protein; D007074:Immunoglobulin G; D020169:Caspases