Desmosomes are adhesive intercellular junctions that act as cell surface attachment sites for intermediate filaments. The desmosomal glycoproteins, desmogleins and desmocollins, are members of the cadherin family of adhesion molecules. In addition, desmoglein has been shown to coimmunoprecipitate with the junctional protein plakoglobin. To characterize further the interaction between plakoglobi...

Adhesion between cells is established by the formation of specialized intercellular junctional complexes, such as desmosomes. Desmosomes contain isoforms of two members of the cadherin superfamily of cell adhesion proteins, desmocollins (Dsc) and desmogleins (Dsg), but their combinatorial roles in desmosome assembly are not understood. To uncouple desmosome assembly from other cell-cell adhesio...

Pemphigus is a rare and debilitating autoimmune blistering disease due to keratinocyte cell-cell detachment (acantholysis). Treatments focus on immune suppression but are often associated with severe side effects, slow onset of action frequent clinical relapses; therefore, innovative non-immunosuppressive therapies needed provide rapid, safer long-lasting responses. Patients’ autoantibodies (PV...

The enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) have both been used for testing of antibodies to desmogleins 1 and 3 (anti-Dsg1 and anti-Dsg3) and for the serologic diagnosis of pemphigus. IIF values and antibody concentrations and profile do not always correlate with a specific clinical phenotype and with the disease activity. The purpose of the present stud...

Alveolar epithelial type 2 cells (AEC2) isolated from hyperoxia-treated animals exhibit increases in both proliferation and DNA damage in response to culture. AEC2 express the zonula adherens proteins E-cadherin, -, - and -catenin, desmoglein, and pp120, as demonstrated by Western blotting. Immunohistochemical analysis of cultured AEC2 showed expression of E-cadherin on cytoplasmic membranes va...

Pemphigus is a life-threatening blistering disorder of the skin and mucous membranes caused by pathogenic autoantibodies to desmosomal adhesion proteins desmoglein 3 (Dsg3) and Dsg1. Mechanisms of antibody pathogenicity are difficult to characterize using polyclonal patient sera. Using antibody phage display, we have isolated repertoires of human anti-Dsg mAbs as single-chain variable-region fr...

Genetically engineered mice have been essential tools for elucidating the pathological mechanisms underlying human diseases. In the case of diseases caused by impaired desmosome function, mouse models have helped to establish causal links between mutations and disease phenotypes. This review focuses on mice that lack the desmosomal cadherins desmoglein 3 or desmocollin 3 in stratified epithelia...

The integrity of intercellular junctions that form the "terminal bar" in intestinal epithelium is crucial for sealing the intestinal barrier. Whereas specific roles of tight and adherens junctions are well known, the contribution of desmosomal adhesion for maintaining the intestinal epithelial barrier has not been specifically addressed. For the present study, we generated a desmoglein 2 antibo...

It is widely assumed that the coordinate assembly of desmosomal cadherins and plaque proteins into desmosome-typical plaque-coated membrane domains, capable of anchoring intermediate-sized filaments (IF), requires cell-to-cell contacts and a critical extracellular Ca2+ concentration. To test this hypothesis we studied several cell lines grown for years in media with less than 0.1 mM Ca2+ to ste...

The mainstay of treatment of pemphigus vulgaris is systemic corticosteroids. Intravenous immunoglobulins have been reported as an adjuvant corticosteroid-sparing regimen in recalcitrant pemphigus vulgaris. The purpose of the study was to monitor disease activity, serum levels of autoantibodies and doses of oral corticosteroids in 4 patients with recalcitrant pemphigus vulgaris adjuvantly treate...