Hindered transport of macromolecules in isolated glomeruli .1. Diffusion across intact and cell-free capillaries
Hindered transport of macromolecules in isolated glomeruli .1. Diffusion across intact and cell-free capillaries
复制标题
DOI：
10.1016/s0006-3495(97)78659-4
复制
发表时间：
1997-01-01
影响因子：
3.4
通讯作者：
Daniels, BS
中科院分区：
文献类型：
--
作者：
Edwards, A;Deen, WM;Daniels, BS
肾小球毛细血管形成的滤液必须穿过串联排列的一层内皮细胞、肾小球基底膜（GEM）和一层上皮细胞。为了阐明GEM和细胞层对不带电大分子运动的相对阻力，我们测量了完整和无细胞毛细血管对Ficoll狭窄部分的扩散渗透性，斯托克斯-爱因斯坦半径范围为3.0 至 6.2 纳米。从大鼠肾脏中分离出肾小球，并用共聚焦显微镜技术监测荧光素标记的聚蔗糖在单个毛细血管环壁上的扩散。在一半的实验中，首先对肾小球进行处理以去除细胞，留下保留肾小球总体形状且几乎完全由 GEM 组成的骨架。无细胞毛细血管对聚蔗糖的扩散渗透性类似于完整毛细血管的 10 至 20 倍，具体取决于分子大小。考虑到细胞对 GEM 表面的大部分堵塞，计算出 GEM 对完整屏障扩散阻力的贡献为总渗透阻力的 13% 至 26%，并随着分子大小的增加而增加。因此，GEM 的贡献虽然小于细胞的贡献，但也不能忽略不计。最有可能造成扩散阻力的细胞部分是狭缝隔膜，它跨越上皮足突之间的过滤狭缝。开发了一种新颖的流体动力学模型，将狭缝隔膜的扩散阻力与其结构联系起来，该结构被理想化为阶梯状排列的单层圆柱形纤维。
The filtrate formed by renal glomerular capillaries must pass through a layer of endothelial cells, the glomerular basement membrane (GEM), and a layer of epithelial cells, arranged in series, To elucidate the relative resistances of the GEM and cell layers to movement of uncharged macromolecules, we measured the diffusional permeabilities of intact and cell-free capillaries to narrow fractions of Ficoll with Stokes-Einstein radii ranging from 3.0 to 6.2 nm. Glomeruli were isolated from rat kidneys, and diffusion of fluorescein-labeled Ficoll across the walls of single capillary loops was monitored with a confocal microscopy technique. In half of the experiments the glomeruli were treated first to remove the cells, leaving skeletons that retained the general shape of the glomerulus and consisted almost entirely of GEM. The diffusional permeability of cell-free capillaries to Ficoll was similar to 10 to 20 times that of intact capillaries, depending on molecular size, Taking into account the blockage of much of the GEM surface by cells, the contribution of the GEM to the diffusional resistance of the intact barrier was calculated to be 13% to 26% of the total, increasing with molecular size, Thus, the GEM contribution, although smaller than that of the cells, was not negligible, The structure that is most likely to be responsible for the cellular part of the diffusional resistance is the slit diaphragm, which spans the filtration slit between epithelial foot processes, A novel hydrodynamic model was developed to relate the diffusional resistance of the slit diaphragm to its structure, which was idealized as a single layer of cylindrical fibers in a ladder-like arrangement.