Back to Search
Start Over
Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions
- Source :
- The Journal of Cell Biology
- Publication Year :
- 1996
- Publisher :
- ROCKEFELLER UNIV PRESS, 1996.
-
Abstract
- Polymorphonuclear leukocytes (PMN) infiltration into tissues is frequently accompanied by increase in vascular permeability. This suggests that PMN adhesion and transmigration could trigger modifications in the architecture of endothelial cell-to-cell junctions. In the present paper, using indirect immunofluorescence, we found that PMN adhesion to tumor necrosis factor-activated endothelial cells (EC) induced the disappearance from endothelial cell-to-cell contacts of adherens junction (AJ) components: vascular endothelial (VE)-cadherin, alpha-catenin, beta-catenin, and plakoglobin. Immunoprecipitation and Western blot analysis of the VE-cadherin/catenin complex showed that the amount of beta-catenin and plakoglobin was markedly reduced from the complex and from total cell extracts. In contrast, VE-cadherin and alpha-catenin were only partially affected. Disorganization of endothelial AJ by PMN was not accompanied by EC retraction or injury and was specific for VE-cadherin/catenin complex, since platelet/endothelial cell adhesion molecule 1 (PECAM-1) distribution at cellular contacts was unchanged. PMN adhesion to EC seems to be a prerequisite for VE-cadherin/catenin complex disorganization. This phenomenon could be fully inhibited by blocking PMN adhesion with an anti-integrin beta 2 mAb, while it could be reproduced by any condition that induced increase of PMN adhesion, such as addition of PMA or an anti-beta 2-activating mAb. The effect on endothelial AJ was specific for PMN since adherent activated lymphocytes did not induce similar changes. High concentrations of protease inhibitors and oxygen metabolite scavengers were unable to prevent AJ disorganization mediated by PMN. PMN adhesion to EC was accompanied by increase in EC permeability in vitro. This effect was dependent on PMN adhesion, was not mediated by proteases and oxygen-reactive metabolites, and could be reproduced by EC treatment with EGTA. Finally, immunohistochemical analysis showed that VE-cadherin distribution was affected by PMN adhesion to the vessel wall in vivo too. This work suggests that PMN adhesion could trigger intracellular signals in EC that possibly regulate VE-cadherin /catenin complex disorganization. This effect could increase EC permeability and facilitate PMN transmigration during the acute inflammatory reaction.
- Subjects :
- Umbilical Veins
Neutrophils
Blotting, Western
Integrin
Vascular permeability
Biology
Cell junction
Adherens junction
Endopeptidases
Cell Adhesion
Humans
Fluorescent Antibody Technique, Indirect
Cell adhesion
Cells, Cultured
beta Catenin
Cadherin
Articles
Cell Biology
Cadherins
Cell biology
Endothelial stem cell
Cytoskeletal Proteins
Intercellular Junctions
Desmoplakins
Trans-Activators
biology.protein
Endothelium, Vascular
gamma Catenin
Catenin complex
alpha Catenin
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....07b637c4cad6832e66bb79b2d46810d9