and Jürgen Roth2
(1)
Medical University of Vienna, Vienna, Austria
(2)
University of Zurich, Zurich, Switzerland
Continuous Capillary, Weibel-Palade Bodies
The inner lining of blood and lymphatic vessels is a simple, squamous epithelium, designated as “endothelium.” The endothelium performs multiple tasks and is diversely developed according to the different functions in the various segments of the macro- and microvascular systems. It may be tight or more or less open for traffic between the lumen and the tissue outside in one or both directions, with specific transendothelial transport mechanisms existing in capillaries. Capillaries are exchange vessels and can be classified as three main types: continuous capillaries (panels A and B), discontinuous capillaries, and fenestrated types (cf. Figs. 122 and 148, respectively).
Panel A presents a continuous capillary with the complete endothelium (E) and an embracing pericyte. Details of the endothelium are shown in panel B. The adjacent endothelial cells are overlapping. They are in contact and linked to each other (arrows in B) by both tight and adhering junctions. A barrier is formed, which impedes intercellular transport. In continuous capillaries, the multitude of transendothelial traffic including fluids, solutes, and macromolecules occurs by transcellular transport via small vesicles, which are transported in both directions from apical to basolateral cell surfaces and vice versa. In the endothelial cells shown in panels A and B, numerous caveolae are visible close to the cell surfaces, and small transport vesicles are abundant in the cytoplasm. There is evidence that the endothelial barrier function is regulated in part by the transcellular transport of albumin and other macromolecules via caveolae (cf. Fig. 63). In microvascular endothelial cells, interactions between a 60-kDa endothelial cell surface albumin-binding protein and caveolin-1 have been identified being supposed to activate signalling pathways eventually leading to vesicle formation and transendothelial vesicle transport. Other proteins, such as transferrin, are transported via clathrin-dependent mechanisms (cf. Fig. 58). The endothelial cells form prominent basal processes, which in places accompany the capillary and build up a second endothelial layer between the basal lamina and the pericyte (panel A). The complete endothelial part of the capillary is surrounded by a continuous basal lamina (arrowheads in A and B), which also continuously covers the surface of the pericyte embracing the endothelium.
Within endothelial cells, a number of bioactive substances including hormones, adhesive molecules, and factors of the coagulation system, are stored and, upon disturbance, are promptly delivered to the surface of the cells. By this mechanism, endothelial cells are able to change the microenvironment of perturbed regions and modulate and control inflammatory and hemostasis processes. The insets in panel B show endothelial cell-specific storage vesicles, the Weibel-Palade bodies, in cross section and longitudinal section (insets 1 and 2, respectively). In both, the typical tubular substructures are visible. Weibel-Palade bodies represent the storage compartments for von Willebrand factor, which has a pivotal role in controlling adhesion and aggregation of platelets at sites of vascular injury. Recently, new insights into the biogenesis of Weibel-Palade bodies, mechanisms of their release from the endothelial cells, and remodeling of von Willebrand factor during exocytosis have been provided by advanced microscopic technologies, including cryo-methods and three-dimensional analyses.
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