Transcellular vesicular transport in epithelial and endothelial cells: Challenges and opportunities

Abstract

Vesicle‐mediated transcellular transport or simply “transcytosis” is a cellular process used to shuttle macromolecules such as lipoproteins, antibodies, and albumin from one surface of a polarized cell to the other. This mechanism is in contrast to the transit of small molecules such as anions, cations and amino acids that occur via uptake, diffusion through the cytosol and release and is also distinct from paracellular leak between cells. Importantly, transcytosis has evolved as a process to selectively move macromolecules between 2 neighboring yet unique microenvironments within a multicellular organism. Examples include the movement of lipoproteins out of the circulatory system and into tissues and the delivery of immunoglobulins to mucosal surfaces. Regardless of whether the transport is conducted by endothelial or epithelial cells, the process often involves receptor‐mediated uptake of a ligand into an endocytic vesicle, regulated transit of the carrier through the cytoplasm and release of the cargo via an exocytic event. While transcytosis has been examined in detail in epithelial cells, for both historical and technical reasons, the process is less understood in endothelial cells. Here, we spotlight aspects of epithelial transcytosis including recent findings and review the comparative dearth of knowledge regarding the process in endothelial cells highlighting the opportunity for further study.

Transcytosis route mediates rapid delivery of intact antibodies to draining lymph nodes

“…Since macrophages were not involved in the antibody transfer, we next focused on the potential role of LECs in the uptake of antibodies. Certain macro molecules can be shuttled from one surface of the cell to the other by transcellular vesicular transport, i.e., transcytosis (15,(25)(26)(27)(28)(29)(30). We found that the extremely attenuated (often <200 nm in thick ness) cytoplasmic projections of sinusoidal LECs are very rich in heterogeneous cytoplasmic vesicles resembling flaskshaped cav eolae, round intracytoplasmic vesicles, and elongated tubulovacu olar structures ( Figure 7A).…”

Three-Dimensional Microscopy Demonstrates Series and Parallel Organization of Human Peripapillary Capillary Plexuses

“…34 In addition to pericytes, this buffering property may be aided by the uneven expression of proteins and enzymes involved in transcellular endothelial transport across the ICP, such as the Rho family of GTPases, the claudin family of proteins, and a broad range of cytokines, including IL-1, IL-4, IL-10, and IL-10. 35 We emphasize that the above hypotheses were not specifically investigated in the present study and require further research for clarification. Other reasons that may explain the variations in capillary circulation morphology between retinal layers may relate to their distinct role in heat exchange, retinal thermal regulation, and maintaining immune privilege.…”

Endothelial Transcytosis of Lipoproteins in Atherosclerosis

“…The transport of macromolecules, including lipoproteins, across the endothelium is actively controlled by ECs via the transcellular route, or transcytosis ( 5 , 6 ). The process of transcytosis involves fluid phase or receptor-mediated ligand uptake by endocytosis, transition of the cargo through the cytoplasm, and exocytic release of the cargo ( 7 ).…”