Permeability characteristics of microvascular walls.

Blood to lymph transport of macromolecules has been modeled by assuming a rather numerous population of small pores and a considerably smaller population of large pores across the microvascular walls. Such "black box" studies, however, are inherently incapable of identifying the precise pathways of movement. Electron microscopy has shown a variety of structures which might be identified as the "pores". These include the intercellular junctions; vesicles which may shuttle across the endothelial cells; chains of vesicles forming open pathways; and, in the case of fenestrated capillaries, the fenestrae. With the exception of the shuttling vesicles, these structures have generally been thought to be relatively static, representing a part of the architecture of the normal cell, albeit varying from organ to organ. Arterioles, capillaries and venules have been shown to have differing transport properties. Three possible barriers to transport are now recognized; a fibrous layer on the surface of the endothelial cells; the endothelial cells themselves; and the basement membrane. Three properties of the macromolecule appear to be important in determining its ease of transmural passage; its size; its charge; and its chemical constitution. The simple "shuttling" model of transport by means of vesicles has recently been seriously questioned, and does not appear to be adequate to explain macromolecular transport. More and more evidence is accumulating to indicate that the chemical nature of the macromolecule is of considerable importance in determining whether or not it will transit the microvascular wall. Evidence will be shown that macromolecular transport is largely, if not entirely, a biochemically stimulated set of dynamic events, rather than being explicable on the basis of passive diffusion processes. The current state of our knowledge of these aspects of the problem of macromolecular transport are discussed, and suggestions made as to how to resolve some of the questions still unanswered.