Role of claudin interactions in airway tight junctional permeability
Role of claudin interactions in airway tight junctional permeability
复制标题
DOI：
10.1152/ajplung.00182.2003
复制
发表时间：
2003-11-01
影响因子：
4.9
通讯作者：
Johnson, LG
中科院分区：
文献类型：
--
作者：
Coyne, CB;Gambling, TM;Johnson, LG
气道上皮紧密连接（TJ）用于分离肺的外部和内部环境。然而，调节这种功能的密蛋白家族成员尚未完全阐明。我们的特点是在肺移植过程中从人供体中取出的正常气道中的claudin表达，并确定每个claudin对气道屏障功能的贡献。构建NIH/3 T3和人气道（IB3.1）细胞中的稳定细胞系，其表达在人气道中发现的紧密连接蛋白组分紧密连接蛋白-1、紧密连接蛋白-3或紧密连接蛋白-5。评估了claudin表达对跨上皮阻力、渗透系数和claudin-claudin相互作用的影响。Claudin-1和-3降低溶质渗透性，而claudin- 5增加渗透性。我们还在细胞系和新鲜切除的人气道中检测到claudin- 5的寡聚化。免疫共沉淀研究揭示了细胞系和人气道上皮中claudin物种之间的异嗜性相互作用。这些表明，气道TJs由赋予连接选择性的密蛋白-密蛋白相互作用调节。
Airway epithelial tight junctions (TJs) serve to separate the external and internal environments of the lung. However, the members of the claudin family that mediate this function have not been fully delineated. We characterized the claudin expression in normal airways removed from human donors during lung transplantation and determined the contribution of each claudin to airway barrier function. Stable cell lines in NIH/3T3 and human airway (IB3.1) cells were constructed expressing the claudin components found in the human airway, claudin-1, -3, or -5. The effects of claudin expression on transepithelial resistance, permeability coefficients, and claudin-claudin interactions were assessed. Claudin-1 and -3 decreased solute permeability, whereas claudin- 5 increased permeability. We also detected oligomerization of claudin- 5 in cell lines and in freshly excised human airways. Coimmunoprecipitation studies revealed heterophilic interactions between claudin species in both cell lines and human airway epithelium. These suggest that airway TJs are regulated by claudin-claudin interactions that confer the selectivity of the junction.