Sharma R, Sharma M, McCarthy E T, Ge X L, Savin V J
Department of Medicine, Division of Nephrology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Kidney Int. 2000 Nov;58(5):1973-9. doi: 10.1111/j.1523-1755.2000.00369.x.
Sera from some patients with focal segmental glomerulosclerosis (FSGS) increase glomerular albumin permeability (P(alb)) in vitro. The hypothesis that a component of normal serum can protect the glomerular permeability barrier was tested using sera from FSGS patients, normal individuals, and several mammalian and avian species.
In most experiments, isolated rat glomeruli were incubated in medium containing FSGS serum known to increase P(alb) in vitro, normal serum, or both active FSGS and normal serum. In other experiments, fractions of normal serum and serum from other vertebrate species were incubated with active FSGS serum. P(alb) was calculated from glomerular capillary expansion in response to an oncotic gradient. To enrich the blocking activity, normal pooled human plasma was subjected to various biochemical manipulations.
Normal human serum prevented the increase in P(alb) (active FSGS sera, 0.77 +/- 0.12; active FSGS sera:normal serum, 1:1 mix, 0.06 +/- 0.30, P < 0.001). Protection diminished as the concentration of normal serum was decreased. Specific fractions of human serum, including human albumin and immunoglobulin fractions, were not protective. Blocking activity was present in 80% ammonium sulfate precipitate and certain fractions from size-exclusion chromatography of normal pooled human plasma. Normal serum from each of the vertebrate species tested also prevented the increase in P(alb). Preincubation with normal serum was protective during subsequent incubation with FSGS serum, but normal serum was not protective after preincubation with FSGS serum.
We conclude that a factor or factors in normal serum block the permeability effect of active FSGS sera. This phenomenon may account for variability in proteinuria among patients with FSGS and may explain inconsistent proteinuria following injection of FSGS sera into experimental animals. Characterization of the protective substance(s) and the mechanism by which the increase in permeability is blocked may provide insight into the pathogenesis of FSGS.
一些局灶节段性肾小球硬化（FSGS）患者的血清在体外可增加肾小球白蛋白通透性（P(alb)）。我们使用FSGS患者、正常个体以及几种哺乳动物和鸟类的血清，对正常血清中的一种成分可保护肾小球通透性屏障这一假说进行了验证。
在大多数实验中，将分离的大鼠肾小球置于含有已知能在体外增加P(alb)的FSGS血清、正常血清或活性FSGS血清与正常血清二者的培养基中孵育。在其他实验中，将正常血清及其他脊椎动物物种血清的组分与活性FSGS血清一起孵育。根据肾小球毛细血管因胶体渗透压梯度而发生的扩张来计算P(alb)。为富集阻断活性，对正常混合人血浆进行了各种生化处理。
正常人血清可防止P(alb)升高（活性FSGS血清，0.77±0.12；活性FSGS血清与正常血清按1:1混合，0.06±0.30，P<0.001）。随着正常血清浓度降低，保护作用减弱。人血清的特定组分，包括人白蛋白和免疫球蛋白组分，无保护作用。80%硫酸铵沉淀以及正常混合人血浆经尺寸排阻色谱法分离得到的某些组分具有阻断活性。所检测的每种脊椎动物物种的正常血清也可防止P(alb)升高。在随后与FSGS血清孵育期间，用正常血清预孵育具有保护作用，但在与FSGS血清预孵育后，正常血清无保护作用。
我们得出结论，正常血清中的一种或多种因子可阻断活性FSGS血清的通透性效应。这种现象可能解释了FSGS患者蛋白尿的变异性，并可解释向实验动物注射FSGS血清后蛋白尿不一致的现象。对保护性物质及其阻断通透性增加的机制进行表征，可能有助于深入了解FSGS的发病机制。
