Regulation of pulmonary endothelial cell permeability
Intercellular junctions in endothelial cells include tight junctions, adherens junctions and gap junctions. Also important in endothelial integrity are focal adhesion contacts between endothelial cells and extracellular matrix. All of these contacts but gap junctions are closely associated with the actin cytoskeleton by specific connector proteins. Increasing understanding of these interactions show that these systems have tightly regulated and dynamic responses to stimuli.
In addition to contracture, endothelial cell junctions are opened by alterations in the junctional maintenance proteins involved in tight and adherens junctions between cells and focal adhesion plaques between cell and matrix Lum 1996). Cell and matrix junctions are linked to the actin based cytoskeleton through structural proteins including vinculin, and actinin. Tight junctions are maintained by endothelial cell zonula occludens protein (ZO-1) interacting with the membrane surface protein occludin. Adherens junctions are associated with cadherin transmembrane linking proteins tied to catenins which interact with actin linking proteins. Focal adhesion contacts use integrin mediated attachment to a variety of extracellular matrix proteins and are apparently connected to the actin cytoskeleton through linking proteins interacting with paxillin, talin and the intercellular integrin domains. Modulation of cell junctions in response to permeability agonists occurs through phosphorylation reactions of linking proteins. These include phosphorylation of vinculin, release of ß catenin and dephosphorylation of p125fak protein kinase in focal adhesions
Opening Endothelial Cell Junctions
In Normal EC (A), ZO-I Protein completely encircles the borders of cultured cells. Cells stimulated to open their junctions (B) retract ZO-I and open gaps between cells.