Role of Caveolin-1 in the Regulation of Pulmonary Endothelial Permeability

Abstract

Endothelial permeability measurements of intact vascular beds and monolayer cultures are used to describe transport of small molecules (ions, water, and nutrients), macromolecules and plasma protein across the vascular endothelia. Disruption of the endothelial barrier leads to vascular hyper­permeability and protein-rich edema which is a key hallmark of inflammation. Transport of the most abundant plasma protein, albumin, occurs by means of transcellular and paracellular pathways. In healthy, noninflamed vessels, endothelial cell–cell contacts significantly restrict the paracellular permeability of albumin, whereas its transcellular transport from the blood to the abluminal perivascular interstitium occurs via caveolae. Thus, caveolae-mediated transport is a primary determinant of the basal endothelial permeability properties. Increased paracellular permeability induced during inflammation is thought to be due to the opening of interendothelial cell–cell junctions and disruption of endothelial cell–matrix contacts within the vasculature. We recently demonstrated that caveolae-mediated transendothelial transport (transcytosis) of macromolecules through the microvascular endothelial barrier is also an important mechanism responsible for inflammation-evoked pulmonary vascular hyperpermeability and protein-rich edema formation. Moreover, caveolin-1, a structural and scaffolding protein required for caveolae formation and transcellular transport, also plays an important role in oxidant-induced paracellular hyperpermeability. This review highlights the methods used to assess transcellular and paracellular permeability properties of the intact mouse lung and cultured endothelial cell monolayers.