Endothelial Barrier Dynamics: Studies in a Cell-Column Model of the Microvasculature

Abstract

Endothelial cells form continuous monolayers that restrict the transport of solutes across the endothelial layer (Renkin, 1952; Simionescu, 1983; Albelda et al., 1988; Haselton et al., 1989, 1992a, 1992b). Experimental evidence continues to accumulate in support of the hypothesis that the endothelial cell monolayer lining the intravascular space is an important determinant of normal transcapillary barrier. The majority of transendothelial solute exchange appears to take place para-cellularly and is thought to occur at interendothelial junctions (Shasby et al., 1982; Shasby and Shasby, 1986; Haselton et al., 1989, 1992). Many physiological agents modify the endothelial barrier, but maintenance and regulation of solute transport across the endothelium remains poorly understood. In vivo measurements of microvascular transcapillary permeability are difficult to obtain and quantify. One of the principal difficulties is that, as in other microvascular systems, the measurement of microvascular permeability can be affected by changes in capillary recruitment and/or hydrostatic pressure. For these reasons, investigators have sought to study vascular barrier maintenance and regulation in vitro. One of the approaches that has proven useful is the in vitro investigations of the properties of cultured endothelium. A key property of endothelium that makes these studies feasible is that, with the proper substrate conditions, in vitro endothelial cells retain their in vivo growth characteristics and form confluent monolayers. One method of investigation that has proven useful is the study of the dynamic properties of the endothelial in vitro transport barrier through the use of systems that detect and quantify changes in endothelial monolayer permeability.