Capillary endothelial surface layer selectively reduces plasma solute distribution volume

Capillary endothelial surface layer selectively reduces plasma solute distribution volume
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DOI:
10.1152/ajpheart.2000.278.1.h285
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发表时间:
2000-01-01
影响因子:
4.8
通讯作者:
Duling, BR
Duling, BR
中科院分区:
医学2区
文献类型:
--
作者:
Vink, H;Duling, BR

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我们以前报道,0.4- 0.5 μ m厚的内皮细胞表面层限制右旋糖酐70(70 kDa)的仓鼠提睾肌毛细血管的中央核心。在本研究中,我们使用了各种血浆示踪剂,以探测的屏障性能的内皮细胞表面层,结合荧光和明场活体显微镜。对于大于或等于70 kDa的中性或阴离子葡聚糖,没有观察到内皮表面层的渗透,但是对于中性葡聚糖40(40 kDa)和中性游离染料,没有观察到内皮表面层的渗透。(罗丹明,0.4 kDa)在1分钟内与内皮表面层平衡。(0.4-40 kDa)相对缓慢地渗透内皮表面层:半衰期(tau(50))在11和60分钟之间,这取决于示踪剂的大小。此外,两种血浆蛋白,纤维蛋白原(340 kDa)和白蛋白(67 kDa),缓慢移动到内皮细胞:表面层在相同的速度,尽管有很大的不同大小(tau(50)约40分钟)。在这些实验过程中不进入糖萼的右旋糖酐70在与白蛋白缀合时以与游离白蛋白相同的速率进入。这些发现表明,对于阴离子分子的大小和电荷有一个深刻的影响渗透到糖萼的速度。不同蛋白质分子对糖萼的渗透率相等,表明多种因素可能影响屏障的渗透,包括分子大小、电荷和结构。
We previously reported that a 0.4- to 0.5-mu m-thick endothelial surface layer confines Dextran 70 (70 kDa) to the central core of hamster cremaster muscle capillaries. In the present study we used a variety of plasma tracers to probe the barrier properties of the endothelial surface layer using combined fluorescence and brightfield intravital microscopy. No permeation of the endothelial surface layer was observed for either neutral or anionic dextrans greater than or equal to 70 kDa, but a neutral Dextran 40 (40 kDa) and neutral free dye (rhodamine, 0.4 kDa) equilibrated with the endothelial surface layer within 1 min. In contrast, small anionic tracers of similar size (0.4-40 kDa) permeated the endothelial surface layer relatively slowly with: half-times (tau(50)) between 11 and 60 min, depending on tracer size. Furthermore, two plasma proteins, fibrinogen (340 kDa) and albumin (67 kDa), moved slowly into the endothelial:surface layer at the same rates, despite greatly differing sizes (tau(50) approximate to 40 min). Dextran 70, which did not enter the glycocalyx over the course of these experiments, entered at the same rate as free albumin when it was conjugated to albumin. These findings demonstrate that for anionic molecules size and charge have a profound effect on the penetration rate into the glycocalyx. The equal rates of penetration of the glycocalyx demonstrated by the different protein molecules suggests that multiple factors may influence the penetration of the barrier, including molecular size, charge, and structure.