Structure and permeability in human placental capillaries

Abstract

Summary Capillaries in the human and guinea pig placenta closely resemble those of cardiac and skeletal muscle both in their continuous endothelium and in their relatively high restrictiveness to permeation by macromolecules. Their detailed paracellular junctional architecture not only closely resembles other continuous capillaries, but has served as an important model for the investigation of major questions about the subcellular and molecular basis of capillary permeability. In such capillaries the main site for transendothelial water and solute flows and for imposition of molecular size restriction appears to be the paracellular clefts of the endothelium. Within these clefts the discontinuous tight junctions, which show extensive molecular homology with epithelial junctions, may be rate-limiting for hydraulic conductivity but are not size-limiting for permeability of hydrophilic solutes. It is likely that the main sites of size restriction are adhesion belts of the paracellular cleft, where a likely filtering structure is the linker array which is rich in the endothelium-specific adhesion molecule VE-cadherin. An important area for experiments in the next few years will be the identification of the cellular signals involved in the regulation of endothelial permeability which lead to repositioning of the adhesion molecules of the paracellular cleft.