Localization of 7H6 tight junction-associated antigen along the cell border of vascular endothelial cells correlates with paracellular barrier function against ions, large molecules, and cancer cells

Localization of 7H6 tight junction-associated antigen along the cell border of vascular endothelial cells correlates with paracellular barrier function against ions, large molecules, and cancer cells
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DOI:
10.1006/excr.1996.0034
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发表时间:
1996-02-01
影响因子:
3.7
通讯作者:
Mori, M
Mori, M
中科院分区:
医学3区
文献类型:
--
作者:
Satoh, H;Zhong, Y;Mori, M

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为了研究内皮屏障的调节,我们采用跨内皮电阻(TER)、白蛋白和葡聚糖的流量、大鼠乳腺癌(SST-2)细胞跨大鼠肺内皮(RLE)细胞的迁移、以7 H6抗原的免疫细胞化学表达为指标。以汇合细胞密度培养的RLE细胞不表达化学上可证实的7 H6抗原,并且具有低的细胞旁屏障功能。然而,用0.5 mM二丁酰cAMP或10(-6)M全反式维甲酸处理内皮细胞4天,诱导7 H6抗原优先在细胞边界,同时增强屏障功能的两倍,在TER和流量的白蛋白和葡聚糖。此外,RA处理的RLE细胞单层具有增强的屏障功能,显著抑制SST-2细胞的迁移。这些结果与我们以前的研究表明,7 H6抗原不仅在上皮细胞,而且在血管内皮细胞的细胞旁屏障功能的调节中具有至关重要的作用。本研究还表明,血管内皮细胞的紧密连接在体内起着血液和组织之间对抗转移性癌细胞的屏障的作用。(C)出版社:Academic Press,Inc.
To study the regulation of the endothelial barrier, we examined the relationship between the paracellular barrier function and the expression of 7H6 antigen localized at tight junctions of endothelial cells by using transendothelial electrical resistance (TER), fluxes of albumin and dextran, transmigration of rat mammary cancer (SST-2) cells across rat lung endothelial (RLE) cells, and immunocytochemical expression of 7H6 antigen as parameters. RLE cells cultured at a confluent cell density did not express immunohistochemically demonstrable 7H6 antigen and had low paracellular barrier functions. However, treatment of the endothelial cells with 0.5 mM dibutyryl-cAMP or 10(-6) M all-trans-retinoic acid for 4 days induced 7H6 antigen preferentially at the cell border and simultaneously enhanced the barrier function twofold, in terms of TER and fluxes of albumin and dextran. Furthermore, RA-treated RLE cell monolayers with the enhanced barrier function significantly inhibited the transmigration of SST-2 cells. These results together with those of our previous study indicate that 7H6 antigen has a crucial role in the regulation of paracellular barrier function not only in epithelial cells but also in vascular endothelial cells. The present study also suggests that tight junctions of vascular endothelium in vivo function as a barrier between blood and tissues against metastatic cancer cells. (C) 1996 Academic Press, Inc.