Transcytosis capillary endothelial cells

Many dissolved proteins that have been transported through the alveolar cells are rapidly reabsorbed into the blood through the capillary endothelial cells (also by transcytosis). In the case of some large proteins, they are more slowly drained across the interstitial space by means of the pulmonary lymphatics, which also empty into the bloodstream via the thoracic duct and superior vena cava. 

Most electron microscopic studies of BBB endothelial cells suggest the presence of relatively few observable endocytic vesicles in the cytoplasm of these cells compared with other endothelia. For example, the BBB contains only a fifth to a sixth of the endocytic profiles seen in muscle capillary endothelia [54], although they may increase to comparable levels with inflammation of the BBB [55]. However, when a comparison is made of the ability of capillary endothelia in a variety of different tissues to trancytose protein, there is a very poor correlation between the protein permeability of a microvessel and the number of observable endocytic profiles [54]. Brain capillary endothelia are very thin cells, the luminal and ablum-inal membranes only being separated by some 500 nm or less (5000 A), and caveoli are 50-80 nm in diameter and thus the events of transcytosis may be difficult to capture within the cell using conventional electron microscopical techniques. 

Fig. 3. Transvascular exchange. Transport pathways in normal capillary endothelium. (1) endothelial cell (2) lateral membrane diffusion (3) interendothelial junctions—(a) narrow, (b) wide (4) endothelial fenestrae—(a) closed, (b) open (5) vesicular transport—(a) transcytosis, (b) transendothelial channels. Note that water and lipophilic solutes share pathways (1), (3), and (4). Lipophilic solutes may use pathway (2) as well. Hydrophilic solutes and macromolecules use pathways (3) and (4). Macromolecules may also follow pathway (5). Note that in tumors these pathways have a leakier structure. [From Jain (1987a), with permission.]...

Several strategies for increasing the permeability of the brain capillaries to proteins have been developed. The permeability of the BBB can be transiently increased by intra-arterial injection of the solutions with high osmolarity, which disrupts inter-endothelial tight junctions [11]. Certain protein modifications, such as cationization by hexamethyldiamine [12] and anionization by succinylation [13], produce enhanced uptake in the brain. Modification of drugs [14] and proteins [15] by linkage to an anti-transferrin receptor antibody also appears to enhance transport into the brain. This approach depends on receptor-mediated transcytosis of transferrin-receptor complexes by brain endothelial cells substantial uptake also occurs in the liver. 

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