Inflammatory mediators induce sequestration of VE-cadherin in cultured human endothelial cells

The mechanisms through which inflammatory mediators modify endothelial junctional structure are not well understood. Endothelial cells exposed to 1 mM H2O2, 0.1 mM histamine or 4 mM EDTA displayed decreased amounts of VE-cadherin on the cell surface in a time-dependent manner. H2O2 and EDTA-treated...

Full description

Saved in:
Bibliographic Details
Published inInflammation Vol. 24; no. 2; pp. 99 - 113
Main Authors Alexander, J S, Alexander, B C, Eppihimer, L A, Goodyear, N, Haque, R, Davis, C P, Kalogeris, T J, Carden, D L, Zhu, Y N, Kevil, C G
Format Journal Article
LanguageEnglish
Published United States Springer Nature B.V 01.04.2000
Subjects
Antigens, CD
Cadherins - drug effects
Cadherins - metabolism
Carbazoles - pharmacology
Cells, Cultured - chemistry
Cytochalasin D - pharmacology
Cytoskeleton - metabolism
Edetic Acid - pharmacology
Endothelium, Vascular - cytology
Enzyme Inhibitors - pharmacology
Flavonoids - pharmacology
Histamine - pharmacology
Humans
Hydrogen Peroxide - pharmacology
Indoles - pharmacology
Inflammation Mediators - pharmacology
Membrane Proteins - metabolism
Protein Binding
Time Factors
Umbilical Veins - cytology
Online AccessGet full text

Cover

More Information
Summary:The mechanisms through which inflammatory mediators modify endothelial junctional structure are not well understood. Endothelial cells exposed to 1 mM H2O2, 0.1 mM histamine or 4 mM EDTA displayed decreased amounts of VE-cadherin on the cell surface in a time-dependent manner. H2O2 and EDTA-treated cells showed a sustained reduction in surface VE-cadherin, but histamine (0.1 mM) decreased cell surface VE-cadherin only at 5 and 15 min, not at 30 and 60 min. Sequestering of VE-cadherin could also be visualized as a decrease in immunofluorescent labeling of endothelial junctions in fixed, non-extracted monolayers. However, junctional staining was observed in these cells after membrane extraction. This decreased surface expression of VE-cadherin was actin-filament, but not PKC/MAP kinase dependent. VE-cadherin binding to the cytoskeleton was decreased by EDTA, but was not diminished by histamine or H2O2. Therefore, by promoting sequestration of junctional cadherins, inflammatory mediators may decrease adhesive bonds between apposed endothelial cells and increase solute permeability.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0360-3997
1573-2576
DOI:10.1023/A:1007025325451