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Cell Signaling in Vascular Inflammation pp 73–90Cite as

Regulation of Endothelial Barrier Function

Contributions of the Transcellular and Paracellular Pathways

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Abstract

The vascular endothelium, consisting of a monolayer of endothelial cells and extracellular matrix, represents the major barrier to exchange of liquid and solutes across the vessel wall. Thus, minute changes in the endothelial monolayer with respect to its permeability to plasma proteins can have marked effects on the tissue fluid balance and can lead to edema. The paracellular and transcellular pathways control endothelial barrier function. Under physiological conditions, the endothelial barrier is described as being restrictive in that only small molecules (<3 nm) can move through the barrier via the paracellular route, whereas macromolecules are actively transported via the transcellular pathway. This restrictive barrier is required to establish the transendothelial oncotic pressure gradient that maintains tissue fluid homeostasis. Endothelial permeability to albumin, the main plasma protein, is the primary determinant of the oncotic pressure gradient and hence maintains the barrier function of the endothelium. The transcellular pathway, by transporting albumin through the endothelial cell, contributes to maintenance of the barrier function of the endothelium. This pathway is comprised of cargo-containing plasmalemmal vesicles, the caveolae. Recent data indicate that the formation, fission, and transport of caveolae in endothelial cells are dynamic processes that are regulated by coherent actions of the albumin-binding proteins caveolin-1 and dynamin. The activity of these proteins is positively regulated by Src-mediated phosphorylation. Pro-inflammatory mediators and growth factors, by binding endothelial cell-surface receptors, initiate a series of events that lead to the opening of intercellular junctions, thereby allowing passage of albumin across the endothelial monolayer by the paracellular route, disrupting the barrier function of the endothelium. Activation of the small-guanosine-5′-triphosphate (GTP)-binding protein RhoA has been shown to play a primary role in regulating paracellular permeability by modulating the integrity of the intercellular junctional protein complexes. This review focuses on the distinct contributions of caveolae-mediated transcellular and Rhomediated paracellular pathways and their respective roles in regulating endothelial permeability.

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Authors and Affiliations

  1. Department of Pharmacology, University of Illinois at Chicago, Chicago, IL, USA

    Dolly Mehta PhD, Richard D. Minshall PhD & Asrar B. Malik PhD

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  1. Dolly Mehta PhD
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  2. Richard D. Minshall PhD
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  3. Asrar B. Malik PhD
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Editors and Affiliations

  1. Clinical Physiological Medicine, and Medicine, Columbia University, New York, NY, USA

    Jahar Bhattacharya MBBS, DPhil (Professor of Physiology and Cellular Biophysics) (Professor of Physiology and Cellular Biophysics)

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© 2005 Humana Press Inc., Totowa, NJ

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Mehta, D., Minshall, R.D., Malik, A.B. (2005). Regulation of Endothelial Barrier Function. In: Bhattacharya, J. (eds) Cell Signaling in Vascular Inflammation. Humana Press. https://doi.org/10.1007/978-1-59259-909-7_9

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  • DOI: https://doi.org/10.1007/978-1-59259-909-7_9

  • Publisher Name: Humana Press

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