Transcytosis of macromolecules through lung endothelial cells is the primary route of transport from the vascular compartment into the interstitial space. Endothelial transcytosis is mostly a caveolae-dependent process that combines receptor-mediated endocytosis, vesicle trafficking via actin-cytoskeletal remodeling, and SNARE protein directed vesicle fusion and exocytosis. Herein, we review the current literature on caveolae-mediated endocytosis, the role of actin cytoskeleton in caveolae stabilization at the plasma membrane, actin remodeling during vesicle trafficking, and exocytosis of caveolar vesicles. Next, we provide a concise summary of experimental methods employed to assess transcytosis. Finally, we review evidence that transcytosis contributes to the pathogenesis of acute lung injury. © 2020 American Physiological Society. Compr Physiol 10:491-508, 2020.
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