Rippe Bengt, Rosengren Bert-Inge, Carlsson Ola, Venturoli Daniele
Department of Nephrology, University Hospital, Lund, Sweden.
J Vasc Res. 2002 Sep-Oct;39(5):375-90. doi: 10.1159/000064521.
The relative contribution of transcytosis vs. large pore transport to the passage of macromolecules across microvascular endothelia has been a controversial issue for nearly half a century. To separate transcytosis from 'porous' transport, the transcytosis inhibitors N-ethylmaleimide (NEM) and filipin have been tested in in situ or ex vivo perfused organs with highly conflicting results. In continually weighed isolated perfused organs, where measurements of pre- and post-capillary resistances, capillary pressure and capillary filtration coefficients can be repeatedly performed, high doses of NEM and filipin increased the bulk transport of macromolecules from blood to tissue, despite producing vasoconstriction. By contrast, in in situ perfused organs, marked reductions in the tissue uptake of albumin tracer have been observed after NEM and filipin. When tissue cooling has been employed as a means of inhibiting (active) transcytosis, results have invariably shown a low cooling sensitivity of albumin transport, compatible with passive transendothelial passage of albumin. This observation is further strengthened by the commonly observed dependence of albumin transport upon the capillary pressure and the rate of transcapillary convection. For low-density lipoprotein (LDL), a cooling-sensitive, non-selective transport component has been discovered, which may be represented by filtration through paracellular gaps, lateral diffusion through transendothelial channels formed by fused vesicles, or by transcytosis. From a physiological standpoint there is little evidence supporting active transendothelial transport of most plasma macromolecules. This seems to be supported by studies on caveolin-1-deficient mice lacking plasmalemmal vesicles (caveolae), in which there are no obvious abnormalities in the transendothelial transport of albumin, immunoglobulins or lipoproteins. Nevertheless, specific transport in peripheral capillaries of several hormones and other specific substances, similar to that existing across the blood-brain barrier, still remains as a possibility.
近半个世纪以来，转胞吞作用与大孔运输对大分子穿过微血管内皮的相对贡献一直是一个有争议的问题。为了将转胞吞作用与“多孔”运输区分开来，转胞吞作用抑制剂N-乙基马来酰亚胺（NEM）和制霉菌素已在原位或离体灌注器官中进行了测试，结果却大相径庭。在持续称重的离体灌注器官中，可以反复测量毛细血管前和毛细血管后的阻力、毛细血管压力和毛细血管滤过系数，高剂量的NEM和制霉菌素尽管会引起血管收缩，但却增加了大分子从血液到组织的大量运输。相比之下，在原位灌注器官中，NEM和制霉菌素处理后，白蛋白示踪剂的组织摄取量显著降低。当采用组织冷却作为抑制（主动）转胞吞作用的手段时，结果始终显示白蛋白运输的冷却敏感性较低，这与白蛋白的被动跨内皮通道运输相一致。白蛋白运输通常对毛细血管压力和跨毛细血管对流速率的依赖性进一步强化了这一观察结果。对于低密度脂蛋白（LDL），已经发现了一种对冷却敏感的非选择性运输成分，它可能表现为通过细胞旁间隙的滤过、通过融合囊泡形成的跨内皮通道的侧向扩散或转胞吞作用。从生理学角度来看，几乎没有证据支持大多数血浆大分子的主动跨内皮运输。这似乎得到了对缺乏质膜囊泡（小窝）的小窝蛋白-1缺陷小鼠的研究的支持，在这些小鼠中，白蛋白、免疫球蛋白或脂蛋白的跨内皮运输没有明显异常。然而，几种激素和其他特定物质在外周毛细血管中的特异性运输，类似于血脑屏障中的运输，仍然是一种可能性。
