Changes in desmoglein 1 expression and subcellular localization in cultured keratinocytes subjected to anti-desmoglein 1 pemphigus autoimmunity.
The complexity of pemphigus acantholysis together with the weak expression of desmoglein 1 (Dsg1) in cultured keratinocytes have made the study on the pathogenic action of anti-Dsg1 antibodies quite difficult. The pathophysiology of the acantholytic phenomenon could depend on the reduction of Dsg1 adhesion function occurring after its massive internalization or decrease of its synthesis. Here, we have investigated this hypothesis by using sera of patients having antibodies against Dsg1 or monoclonal anti-Dsg1 antibodies to simulate pemphigus autoimmunity in Dsg1-rich keratinocytes. Similar to pemphigus foliaceus (PF) and vulgaris (PV) sera, monoclonal anti-Dsg1 antibodies induced transient internalization of Dsg1 and reduced the adhesion strength among keratinocytes. However, binding of IgG to Dsg1 did not determine its early depletion from the adhesion complexes but reduced the amount of Dsg1 found in the Triton X-100 soluble pool of proteins. Taken together, our results represent the first demonstration that anti-Dsg1 antibodies induce similar alterations on the subcellular distribution of Dsg1 irrespective of the disease where they come from. Furthermore, the present study provides insight into the mechanisms underlying epithelial blistering observed in the skin type of pemphigus.
Cirillo
Nicola
N
Regional Center on Craniofacial Malformations-MRI, 1st School of Medicine and Surgery, II University of Naples, Naples, Italy. nicola.cirillo@unina2.it
Gombos
Fernando
F
Lanza
Alessandro
A
D000051:Acantholysis / Q000276:immunology* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002451:Cell Compartmentation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D051183:Desmoglein 1 / Q000276:immunology* / Q000378:metabolism; D003896:Desmosomes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000187:drug effects / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism; D046911:Macromolecular Substances / Q000276:immunology / Q000378:metabolism; D010392:Pemphigus / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D021381:Protein Transport / Q000187:drug effects / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D051183:Desmoglein 1; D007074:Immunoglobulin G; D046911:Macromolecular Substances