Effect of cyclic AMP on barrier function of human lymphatic microvascular tubes
Effect of cyclic AMP on barrier function of human lymphatic microvascular tubes
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DOI：
10.1016/j.mvr.2008.02.003
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发表时间：
2008-05-01
影响因子：
3.1
通讯作者：
Tien, Joe
中科院分区：
文献类型：
--
作者：
Price, Gavrielle M.;Chrobak, Kenneth M.;Tien, Joe
本研究探讨了环AMP （cAMP）对人真皮淋巴微血管内皮细胞（LECs）试管体外屏障功能的影响。在基线条件下，LEC管的屏障功能较弱，对牛血清白蛋白和10 kDa右旋糖酐的扩散渗透系数分别为1.4(-0.6)（+0.9）× 10(-6) cm/s和1.7(-0.5)（+0.8）× 10(-6) cm/s（几何平均+/- 95% CI），以及1.2 +/- 0.5（平均95% CI）每毫米的病灶泄漏。暴露于低浓度（3 μ M）细胞渗透的cAMP类似物并没有改变屏障功能。暴露于较高浓度（80和400 μ M）和/或磷酸二酯酶抑制剂Ro-20-1724 （20 μ M）降低了渗透性和局部泄漏的数量，并增加了屏障的选择性。通透性降低伴随着细胞-细胞边界连续ve -钙粘蛋白染色的增加。暴露于I mM 2',5'-二脱氧腺苷（一种腺苷酸环化酶抑制剂）下，不增加渗透性。无论屏障功能强弱，LECs均表达淋巴特异性主转录因子Prox-1。我们的研究结果表明，体外LEC管的渗透性对cAMP的反应方式类似于对微血管渗透性的描述。(c) 2008爱思唯尔公司版权所有。
This work examines the effect of cyclic AMP (cAMP) on the in vitro barrier function of tubes of human dermal lymphatic microvascular endothelial cells (LECs). Under baseline conditions, the barrier function of LEC tubes was weak, with diffusional permeability coefficients to bovine serum albumin and 10 kDa dextran of 1.4(-0.6)(+0.9) x 10(-6) cm/s and 1.7(-0.5)(+0.8) x 10(-6) cm/s (geometric mean +/- 95% CI), respectively, and 1.2 +/- 0.5 (mean 95% CI) focal leaks per mm. Exposure to low concentrations (3 mu M) of a cell-permeant analog of cAMP did not alter the barrier function. Exposure to higher concentrations (80 and 400 mu M) and/or the phosphodiesterase inhibitor Ro-20-1724 (20 mu M) lowered permeabilities and the number of focal leaks, and increased the selectivity of the barrier. Decreased permeabilities were accompanied by an increase in continuous VE-cadherin staining at cell-cell borders. Exposure to I mM 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, did not increase permeabilities. LECs expressed the lymphatic-specific master transcription factor Prox-1, regardless of whether barrier function was weak or strong. Our results indicate that the permeability of LEC tubes in vitro responds to cAMP in a manner similar to that well-described for the permeability of blood microvessels. (c) 2008 Elsevier Inc. All rights reserved.