Functionally specialized junctions between endothelial cells of lymphatic vessels

淋巴系统 紧密连接 淋巴管内皮 封堵器 内皮 细胞生物学 细胞结 生物 VE钙粘蛋白 细胞粘附分子 钙粘蛋白 粘附 内皮干细胞 解剖 化学 细胞 免疫学 体外 生物化学 内分泌学 有机化学
作者
Peter Bałuk,Jonas Fuxe,Hiroya Hashizume,Talia Romano,Erin Lashnits,Stefan Butz,Dietmar Vestweber,Monica Corada,Cinzia Molendini,Elisabetta Dejana,Donald M. McDonald
出处
期刊:Journal of Experimental Medicine [Rockefeller University Press]
卷期号:204 (10): 2349-2362 被引量:913
标识
DOI:10.1084/jem.20062596
摘要

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.
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