The three-dimensional organization of tight junctions in a capillary endothelium revealed by serial-section electron microscopy

Abstract

Estimates of capillary permeability for hydrophilic solutes are generally interpreted in terms of Pappenheimer's pore theory. The intercellular clefts of the capillary endothelium are considered a likely structural equivalent to the postulated system of small hydrophilic pores. However, correlation of permeabilities and cleft structure requires more knowledge of the detailed structure of the tight junctions which appear to obliterate the clefts. In this study the organization of tight junctions in endothelium of rat heart capillaries has been investigated by serial-section electron microscopy. Cross-sectioned intercellular clefts were photographed in a series of 190 consecutive sections (average thickness approximately equal to 40 nm) and in a series of 16 consecutive sections (average thickness approximately equal to 12.5 nm). Seventy-one junctional segments, each extending over 5-32 consecutive sections, were reconstructed. The endothelial junctions were organized as irregular networks of lines of contact between neighboring cells. Six pathways circumventing the lines of contact were followed through the entire junctional region of the clefts providing a tortuous pathway connecting the luminal and abluminal aspects of the clefts. Moreover, the individual lines of contact were provided with discrete discontinuities, apparently 4 nm wide. The observations support the notion that the paracellular pathway in capillary endothelium is permeable not only to small solutes but also to certain macromolecules.