Functionally specialized junctions between endothelial cells of lymphatic vessels
Peter Baluk,Jonas Fuxe,Jonas Fuxe,Hiroya Hashizume,Hiroya Hashizume,Talia Romano,Talia Romano,Erin Lashnits,Erin Lashnits,Stefan Butz,Dietmar Vestweber,Monica Corada,Cinzia Molendini,Elisabetta Dejana,Elisabetta Dejana,Donald M. McDonald,Donald M. McDonald +16 more
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TLDR
It is suggested that fluid enters throughoutInitial lymphatics via openings between buttons, which open and close without disrupting junctional integrity, but most leukocytes enter the proximal half of initial lymphatics.Abstract:
Recirculation of fluid and cells through lymphatic vessels plays a key role in normal tissue homeostasis, inflammatory diseases, and cancer. Despite recent advances in understanding lymphatic function (Alitalo, K., T. Tammela, and T.V. Petrova. 2005. Nature. 438:946–953), the cellular features responsible for entry of fluid and cells into lymphatics are incompletely understood. We report the presence of novel junctions between endothelial cells of initial lymphatics at likely sites of fluid entry. Overlapping flaps at borders of oak leaf–shaped endothelial cells of initial lymphatics lacked junctions at the tip but were anchored on the sides by discontinuous button-like junctions (buttons) that differed from conventional, continuous, zipper-like junctions (zippers) in collecting lymphatics and blood vessels. However, both buttons and zippers were composed of vascular endothelial cadherin (VE-cadherin) and tight junction–associated proteins, including occludin, claudin-5, zonula occludens–1, junctional adhesion molecule–A, and endothelial cell–selective adhesion molecule. In C57BL/6 mice, VE-cadherin was required for maintenance of junctional integrity, but platelet/endothelial cell adhesion molecule–1 was not. Growing tips of lymphatic sprouts had zippers, not buttons, suggesting that buttons are specialized junctions rather than immature ones. Our findings suggest that fluid enters throughout initial lymphatics via openings between buttons, which open and close without disrupting junctional integrity, but most leukocytes enter the proximal half of initial lymphatics.read more
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Structural and functional features of central nervous system lymphatic vessels
Antoine Louveau,Igor Smirnov,Timothy J. Keyes,Jacob D. Eccles,Sherin J. Rouhani,J. David Peske,Noël C. Derecki,David Castle,James Mandell,Kevin S. Lee,Tajie H. Harris,Jonathan Kipnis +11 more
TL;DR: In searching for T-cell gateways into and out of the meninges, functional lymphatic vessels lining the dural sinuses are discovered, which may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.
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Elisabetta Dejana,Elisabeth Tournier-Lasserve,Elisabeth Tournier-Lasserve,Brant M. Weinstein +3 more
TL;DR: This review discusses recent findings derived from basic cell biology, clinical studies, and studies in animal models such as mice and zebrafish and their possible integration in a common picture of human pathologies.
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