Tightening the Barrier

Abstract

Interendothelial junctional clefts have long been supposed to be the major sites at which water and solutes leave the vessel lumen (except in vessels with fenestrated or discontinuous endothelium) to reach extravascular tissue. Pioneering electron microscopy studies by Palade with the Simionescus demonstrated this phenomenon directly, showing that proteins of a molecular diameter up to 20 A could permeate these clefts in capillaries, and rather larger proteins could do so in post-capillary venules. They were also the first, by usng freeze fracture techniques, to show that the extent and complexity of the arrangement of interendothelial junctional proteins varied substantially across the vasculature, in a manner consistent with what was known about vessel permeability: the most complex and extensive junctions are found in arteries and in the small vessels forming the blood–brain barrier, whereas the least complex and extensive are found in post-capillary venules.1–3 However, at that time neither the identity of the major molecular components of the junctions was known nor had anyone begun to consider what mechanisms might lead to this graded variation of endothelial phenotype.