Cytoskeletal rearrangement mediates human microvascular endothelial tight junction modulation by cytokines

Michael S. Blum, Elisabetta Toninelli, James M. Anderson, Maria S. Balda, Jinyao Zhou, Lynn O'Donnell, Ruggero Pardi, Jeffrey R. Bender

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

The tight junction (TJ) is a specialized intercellular structure responsible for the regulation of ionic and macromolecular flux across cell monolayers. Because plasma leakage is believed to occur mainly across the microvasculature, we hypothesized that microvascular endothelial cells (MVEC) may form more intact, regulatable TJ than other endothelial cell (EC) types, allowing further insight into the control of EC permeability. Primary cultures of MVEC monolayers produced transmonolayer electrical resistances (TER) of 120-155 Ω·cm2, ~10 times that of large-vessel EC. Treatment with tumor necrosis factor and interferon-γ caused a 50% decrease in the TER and a striking fragmentation of the basal, continuous interendothelial cell zonula occludens-1 protein (ZO-1) distribution determined by immunofluorescence. Fragmentation was inhibited by cytochalasin D, and confocal microscopy demonstrated a colocalization between F actin and ZO-1. These findings suggest that the F actin cytoskeleton plays a central role in endothelial TJ barrier regulation and that dynamic cytoskeletal alterations may primarily control vascular permeability.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume273
Issue number1 42-1
Publication statusPublished - Jul 1997

Fingerprint

Tight Junctions
Endothelial Cells
Cytokines
Zonula Occludens-1 Protein
Electric Impedance
Actins
Cytochalasin D
Capillary Permeability
Microvessels
Actin Cytoskeleton
Confocal Microscopy
Interferons
Fluorescent Antibody Technique
Permeability
Tumor Necrosis Factor-alpha

Keywords

  • Capillary permeability
  • Endothelium
  • Inflammation
  • Recombinant interferon-γ
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Blum, M. S., Toninelli, E., Anderson, J. M., Balda, M. S., Zhou, J., O'Donnell, L., ... Bender, J. R. (1997). Cytoskeletal rearrangement mediates human microvascular endothelial tight junction modulation by cytokines. American Journal of Physiology - Heart and Circulatory Physiology, 273(1 42-1).

Cytoskeletal rearrangement mediates human microvascular endothelial tight junction modulation by cytokines. / Blum, Michael S.; Toninelli, Elisabetta; Anderson, James M.; Balda, Maria S.; Zhou, Jinyao; O'Donnell, Lynn; Pardi, Ruggero; Bender, Jeffrey R.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 273, No. 1 42-1, 07.1997.

Research output: Contribution to journalArticle

Blum, Michael S. ; Toninelli, Elisabetta ; Anderson, James M. ; Balda, Maria S. ; Zhou, Jinyao ; O'Donnell, Lynn ; Pardi, Ruggero ; Bender, Jeffrey R. / Cytoskeletal rearrangement mediates human microvascular endothelial tight junction modulation by cytokines. In: American Journal of Physiology - Heart and Circulatory Physiology. 1997 ; Vol. 273, No. 1 42-1.
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