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Inflammatory Mediators Induce Sequestration of VE-Cadherin in Cultured Human Endothelial Cells

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Abstract

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.

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Authors and Affiliations

  1. Molecular and Cellular Physiology, LSU Medical Center, 1501 Kings Highway, Shreveport, Louisiana, 71130

    J. Steven Alexander, Brett C. Alexander, Lois Ann Eppihimer, Nathan Goodyear, Raashid Haque, Christopher P. Davis, Ya-nan Zhu & Christopher G. Kevil

  2. Surgery, LSU Medical Center, 1501 Kings Highway, Shreveport, Louisiana, 71130

    Theodore J. Kalogeris

  3. Medicine, LSU Medical Center, 1501 Kings Highway, Shreveport, Louisiana, 71130

    Donna L. Carden

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  1. J. Steven Alexander
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Alexander, J.S., Alexander, B.C., Eppihimer, L.A. et al. Inflammatory Mediators Induce Sequestration of VE-Cadherin in Cultured Human Endothelial Cells. Inflammation 24, 99–113 (2000). https://doi.org/10.1023/A:1007025325451

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