Elsevier

Life Sciences

Volume 64, Issue 21, 16 April 1999, Pages 1941-1953
Life Sciences

Increased permeability of primary cultured brain microvessel endothelial cell monolayers following TNF-α exposure

https://doi.org/10.1016/S0024-3205(99)00139-3Get rights and content

Abstract

TNF-α is a cytokine that produces increased permeability in the peripheral vasculature; however, little is known about the effects of TNF-α on the bloodbrain barrier (BBB). Using primary cultured bovine brain microvessel endothelial cells (BBMEC) as an in vitro model of the BBB, this study shows that TNF-α produces a reversible increase in the permeability of the brain microvessel endothelial cells. The BBMEC monolayers were pre-treated with 100 ngml of TNF-α for periods ranging from 2 to 12 hours. Permeability was assessed using three molecular weight markers, fluorescein (376 MW), fluorescein-dextran (FDX-4400; 4400 MW), and FDX-70000 (MW 70000). The permeability of BBMEC monolayers to all three fluorescent markers was increased two-fold or greater in the TNF-α treatment group compared to control monolayers receiving no TNF-α. Significant changes in permeability were also observed with TNF-α concentrations as low as 1 ngml. These results suggest that TNF-α acts directly on the brain microvessel endothelial cells in a dynamic manner to produce a reversible increase in permeability. Exposure of either the lumenal or ablumenal side of BBMEC monolayers to TNF-α resulted in similar increases in permeability to small macromolecules, e.g. fluorescein. However, when a higher molecular weight marker was used (e.g. FDX-3000), there was a greater response following lumenal exposure to TNF-α. Together, these studies demonstrate a reversible and time dependent increase in brain microvessel endothelial cell permeability following exposure to TNF-α. Such results appear to be due to TNF's direct interaction with the brain microvessel endothelial cell.

References (27)

  • Y. Fong et al.

    Clin Inimunol and Immunopath

    (1990)
  • M.B. Hansen et al.

    J. Immuno. Meth.

    (1989)
  • C.S. Abraham et al.

    Neurosci. Lett.

    (1996)
  • E.G. Gutierrez et al.

    J. Neuroimmunol.

    (1993)
  • A. Saija et al.

    Life Sciences

    (1995)
  • H. Fillit et al.

    Neurosci. Lett.

    (1991)
  • E. Bonmann et al.

    Neurosci Lett

    (1997)
  • K.L. Audus et al.

    Transport of Macromolecules Across the Capillary Endothelium

  • H. Gerlach et al.

    Annu. Rev. Med.

    (1990)
  • V. Quagliarello et al.

    New Eng. J. Med.

    (1992)
  • M.K. Sharief et al.

    New Eng. J. Med.

    (1991)
  • L.M.E. Grmaldi et al.

    Ann. Neurol.

    (1991)
  • K.S. Kim et al.

    Lymphokine and Cytokine Res.

    (1992)
  • Cited by (0)

    View full text