Functionally specialized junctions between endothelial cells of lymphatic vessels

By P. Baluk, J. Fuxe, H. Hashizume, T. Romano, Erin Lashnits, S. Butz, D. Vestweber, M. Corada, Cinzia Molendini, E. Dejana and 1 more. Journal of Experimental Medicine, 2007

958 citations recorded by the source corpus.

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.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/2d63a27a2b80ae7cb506c91283e3b3f5f536ee76

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In Molecular Biology

1. H. Wiig
2. M. Swartz
3. K. Alitalo
4. T. Tammela
5. Rakesh K. Jain
6. M. Shibuya
7. N. Ferrara

In Oncology

1. K. Alitalo
2. H. Wiig
3. M. Swartz
4. T. Tammela
5. A. Rot
6. Rakesh K. Jain
7. M. Shibuya

Citations in the corpus

• CCR7 and its ligands: balancing immunity and tolerance (2008, background): “The oak-leaf-shaped endothelial cells of the initial segments of lymphatic vessels are not tightly connected to each other, but rather contain 'buttons' of adherens and tight junctions, which create overlapping flaps between endothelial cell”
• Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer. (2012, background): “As mentioned above, initial lymphatics having overlapping flaps at borders of endothelial cells that junction at the tip but are anchored on the sides by discontinuous buttonlike junctions (32) could act as the proposed primary valve system.”
• Lymphangiogenesis: Molecular mechanisms and future promise. (2010, background): “In contrast to continuous interendothelial junctions in blood vessels, lymphatic capillaries have discontinuous or " buttonlike " junctions (Baluk et al., 2007; Tammela et al., 2007).”