Figure 2.

Evolving concepts of open junctions between lymphatic endothelial cells. (A) Three-dimensional rendering of initial lymphatic reconstructed from transmission electron micrographs. Anchoring filaments link endothelial cells to the surrounding connective tissue. (Panel A from Figure 25 in Leak and Burke 1968b; reprinted, with permission, from Rockefeller University Press © 1968.) (B) Concept of changes in endothelial cell junctions in initial lymphatic. (Top) Normal condition, junctions are closed. (Middle) Moderate edema, slits form between endothelial cells. (Bottom) Severe edema, endothelial cells are fully detached and widely separated from one another. (Panel B from Figure 12.14 in Majno and Joris 1996; reprinted, with permission, from John Wiley © 1996.) (C) Three-dimensional renderings of lymphatic endothelial cell borders based on scanning electron microscopy (SEM) images of initial lymphatics with interstitial pressure at normal level (left), moderately increased (middle), and greatly increased (right). Focal regions of intercellular junction detachment are shown as shaded openings that enlarge as lymphatics dilate. (Panel C from Figure 16 in Castenholz 1987; reprinted, with permission, from the International Society of Lymphology © 1987.) (D) Concept of “expansion” phase, when primary valves are open, lymph enters the initial lymphatic along the hydrostatic pressure gradient and secondary valves are closed to prevent backflow, and “compression” phase, when primary valves are closed, secondary valves are open, and lymph is pushed through the collecting lymphatic. (Panel D is from Figure 7 in Mendoza and Schmid-Schonbein 2003; reprinted, with permission, from the American Society of Mechanical Engineers © 2003.)