Heterogeneity of barrier function in the lung reflects diversity in endothelial cell junctions
Heterogeneity of barrier function in the lung reflects diversity in endothelial cell junctions
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DOI：
10.1016/j.mvr.2007.10.006
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发表时间：
2008-04-01
影响因子：
3.1
通讯作者：
Stevens, Troy
中科院分区：
文献类型：
--
作者：
Ofori-Acquah, Solomon F.;King, Judy;Stevens, Troy
内皮细胞组装独特的屏障，赋予不同血管段特定的渗透性要求。我们检查了肺微血管和动脉内皮细胞，以深入了解节段特异性屏障功能的机制。微血管屏障中的跨内皮电阻明显较高，并且屏障功能降低 50% 需要微血管中细胞松弛素 D 的浓度比动脉屏障高 5 倍。转录谱研究发现，N-钙粘蛋白和活化白细胞粘附分子 (ALCAM) 在微血管中的表达水平高于肺动脉内皮细胞。 ALCAM 在肺泡间隔的微血管内皮细胞中检测到，但在较大肺血管的内皮细胞中未检测到。由于 ALCAM 被募集至肺微血管内皮细胞的细胞连接处，但在肺动脉内皮细胞中仍主要保持在胞质中，因此这种模式保留在培养物中。共聚焦分析显示 ALCAM 位于侧质膜区域，与 N- 和 VE-钙粘蛋白共定位。这一发现得到了免疫共沉淀研究的支持，该研究证明了多个粘附连接蛋白复合物中存在 ALCAM。这些功能、生物物理和分子研究结果表明，粘附连接的专门化是高度限制性内皮屏障的基础，以控制流体流入肺泡空腔。 (c) 2007 Elsevier Inc. 保留所有权利。
Endothelial cells assemble unique barriers that confer specific permeability requirements at different vascular segments. We examined lung microvascular and artery endothelial cells to gain insight into mechanisms for segment-specific barrier functions. Transendothelial electrical resistance was significantly higher in microvascular barriers, and a 50% reduction in barrier function required 5-fold higher concentration of cytochalasin D in the microvascular compared to the arterial barrier. Transcriptional profiling studies identified N-cadherin and activated leukocyte cell adhesion molecule (ALCAM) to be most highly expressed in microvascular than in pulmonary artery endothelial cells. ALCAM was detected in microvascular endothelial cells in the alveolar septum but not in endothelial cells in larger pulmonary vessels in situ. This pattern was retained in culture as ALCAM was recruited to cell junctions in pulmonary microvascular endothelial cells but remained predominantly cytosolic in pulmonary artery endothelial cells. Confocal analysis revealed ALCAM in the lateral plasma membrane domain where it co-localized with N- and VE-cadherin. This finding was supported by co-immunoprecipitation studies demonstrating the presence of ALCAM in multiple adherens junction protein complexes. These functional, biophysical and molecular findings suggest specialization of the adherens junction as a basis for a highly restrictive endothelial barrier to control fluid flux into the alveolar airspace. (c) 2007 Elsevier Inc. All rights reserved.