Role of Caveolin-1 in the Regulation of Pulmonary Endothelial Permeability
Role of Caveolin-1 in the Regulation of Pulmonary Endothelial Permeability
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DOI：
10.1007/978-1-61779-191-8_21
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Hu, Guochang
中科院分区：
文献类型：
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作者：
Sun, Yu;Minshall, Richard D.;Hu, Guochang
完整血管床和单层培养的内皮通透性测量用于描述小分子(离子、水和营养物质)、大分子和血浆蛋白在血管内皮细胞中的运输。内皮屏障的破坏导致血管高通透性和富含蛋白质的水肿，这是炎症的一个关键标志。最丰富的血浆蛋白，白蛋白，通过跨细胞和细胞旁途径进行运输。在健康的非炎症血管中，内皮细胞接触显著限制白蛋白的细胞旁通透性，而白蛋白从血液到血管周围间质的跨细胞转运是通过小凹进行的。因此，小窝介导的转运是决定基础内皮细胞通透性的主要因素。炎症过程中引起的细胞旁通透性增加被认为是由于内皮细胞间连接的开放和血管内内皮细胞基质接触的破坏。我们最近证实，小窝介导的大分子通过微血管内皮细胞屏障的跨内皮运输也是炎症诱发的肺血管高通透性和富含蛋白质的水肿形成的重要机制。此外，小窝形成和跨细胞运输所需的结构和支架蛋白小窝蛋白-1在氧化剂诱导的细胞旁高通透性中也起着重要作用。本综述重点介绍了用于评估完整的小鼠肺和培养内皮细胞单层的跨细胞和细胞旁通透性的方法。
Endothelial permeability measurements of intact vascular beds and monolayer cultures are used to describe transport of small molecules (ions, water, and nutrients), macromolecules and plasma protein across the vascular endothelia. Disruption of the endothelial barrier leads to vascular hyperpermeability and protein-rich edema which is a key hallmark of inflammation. Transport of the most abundant plasma protein, albumin, occurs by means of transcellular and paracellular pathways. In healthy, noninflamed vessels, endothelial cell cell contacts significantly restrict the paracellular permeability of albumin, whereas its transcellular transport from the blood to the abluminal perivascular interstitium occurs via caveolae. Thus, caveolae-mediated transport is a primary determinant of the basal endothelial permeability properties. Increased paracellular permeability induced during inflammation is thought to be due to the opening of interendothelial cell cell junctions and disruption of endothelial cell matrix contacts within the vasculature. We recently demonstrated that caveolae-mediated transendothelial transport (transcytosis) of macromolecules through the microvascular endothelial barrier is also an important mechanism responsible for inflammation-evoked pulmonary vascular hyperpermeability and protein-rich edema formation. Moreover, caveolin-1, a structural and scaffolding protein required for caveolae formation and transcellular transport, also plays an important role in oxidant-induced paracellular hyperpermeability. This review highlights the methods used to assess transcellular and paracellular permeability properties of the intact mouse lung and cultured endothelial cell monolayers.