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Intestinal epithelial barrier integrity requires Desmoglein2‐mediated adhesion
Author(s) -
Schlegel Nicolas,
Meir Michael,
Heupel Wolfgang Moritz,
Germer Christoph Thomas,
Waschke Jens
Publication year - 2010
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.24.1_supplement.1002.30
Subject(s) - tight junction , adherens junction , microbiology and biotechnology , cell junction , cadherin , chemistry , desmosome , desmoglein , enterocyte , paracellular transport , adhesion , biophysics , biology , cell , biochemistry , small intestine , organic chemistry , membrane , permeability (electromagnetism)
The integrity of intercellular junctions in intestinal epithelium is crucial for sealing the intestinal barrier. While specific roles of tight and adherens junctions are well known, the contribution of desmosomal adhesion for maintaining the intestinal epithelial barrier has not been addressed. We generated a desmoglein 2 antibody directed against the extracellular domain (Dsg2 ED) to test whether impaired Dsg2‐mediated adhesion affects intestinal barrier functions in vitro. This antibody was capable to block Dsg2 interaction in cell‐free atomic force microscopy experiments. For in vitro studies of the intestinal barrier we used Caco2 cells following differentiation into enterocyte‐like epithelial monolayers. Application of Dsg2 ED to Caco2 monolayers increased cell dissociation compared to controls. Under similar conditions Dsg2 antibody significantly decreased transepithelial electrical resistance. As revealed by immunostaining, this was due to Dsg2 ED antibody‐induced loss of tight junction proteins from the cell borders. Similar results were obtained using a commercial monoclonal antibody against the extracellular domain of Dsg2 to Caco2 monolayers. Antibody‐induced effects were blocked by absorption experiments. Our data indicate that Dsg2‐mediated adhesion affects tight junction integrity and is required to maintain intestinal epithelial barrier properties.