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Endothelial transcytosis in health and disease

Abstract

The visionaries predicted the existence of transcytosis in endothelial cells; the cell biologists deciphered its mechanisms and (in part) the molecules involved in the process; the cell pathologists unravelled the presence of defective transcytosis in some diseases. The optimistic perspective is that transcytosis, in general, and receptor-mediated transcytosis, in particular, will be greatly exploited in order to target drugs and genes to exclusive sites in and on endothelial cells (EC) or underlying cells. The current recognition that plasmalemmal vesicles (caveolae) are the vehicles involved in EC transcytosis has moved through various phases from intial considerations of caveolae as unmovable sessile non-functional plasmalemma invaginations to the present identification of a multitude of molecules and a crowd of functions associated with these ubiquitous structures of endothelial and epithelial cells. Further understanding of the molecular machinery that precisely guides caveolae through the cells so as to reach the target membrane (fission, docking, and fusion), to avoid lysosomes, or on the contrary, to reach the lysosomes, and discharge the cargo molecules will assist in the design of pathways that, by manipulating the physiological route of caveolae, will carry molecules of choice (drugs, genes) at controlled concentrations to precise destinations.

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Acknowledgements

The authors are grateful to Prof. Nicolae Simionescu who coined the term “transcytosis” and uncovered the concept of “receptor-mediated transcytosis”, based on previous work done together with Prof. George E. Palade and Dr. Maya Simionescu, providing a new avenue and a valuable tool to be exploited in therapeutic delivery of drugs. We are thankful to all scientists working in the field and to our collaborators that contributed to the collection of data presented in this review. The dedicated support of Mrs. Marilena Daju (computer assistance) and Mr. Ovidiu Croitoru (graphic design) is highly appreciated. The work was funded from grants obtained from NIH-USA, European Community, COST Action BM0602, the Romanian Academy and Ministry of Education and Research, Romania.

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Correspondence to Maya Simionescu.

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Simionescu, M., Popov, D. & Sima, A. Endothelial transcytosis in health and disease. Cell Tissue Res 335, 27–40 (2009). https://doi.org/10.1007/s00441-008-0688-3

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Keywords

  • Transcytosis
  • Endothelium
  • Caveolae
  • Plasma proteins
  • Disease