Studies of glomerular basement membrane permeability factor in minimal change nephrotic syndrome

微小病变型肾病综合征（MCNS）的病因不明。许多研究者推测MCNS中淋巴细胞培养产生的血管通透性因子（VPF）可能与大量蛋白尿有关。我们已经证明VPF是由MCNS患者的T淋巴细胞产生的。此外，输注T-淋巴细胞培养上清液从患者MCNS到左肾动脉的大鼠，诱导不仅在大鼠尿中的蛋白尿，但也减少了阴离子位点的肾小球基底膜的肾脏在帽子。为了确定MCNS中释放VPF的T淋巴细胞亚群，对T淋巴细胞、CD 4 ^+细胞或CD 8 ^+细胞富集组分的培养上清进行VPF测定。T淋巴细胞通过尼龙毛柱纯化，用单克隆抗体（抗OKT 4和抗OKT 8抗体）和兔抗CD 4+细胞和CD 8+细胞分离。 ...更多信息 谢谢。在T淋巴细胞或CD 4 ^+细胞富集的培养上清液中发现VPF活性。此外，其活性不被抗IL 1或抗IL 2抗体抑制。这些结果表明，VPF可能不同于IL 1或IL 2等淋巴因子，而是由CD 4 ^+细胞产生的。CD 4 ^+细胞产生VPF与MCNS大量蛋白尿的关系有待进一步研究。其次，有报道指出，肾病患者血清和尿液pI的变化可能是导致蛋白排泄的原因之一。我们从尿液中纯化白蛋白，并通过输注白蛋白来研究大鼠肾脏的pI和肾小球基底膜（GBM）渗透性。结果表明，MCNS患者尿中阴离子白蛋白检出率较低。将阴离子较少的白蛋白输注到大鼠肾脏后，大鼠GBM的负电荷减少，蛋白排泄增加。根据这些结果，推测较少的阴离子白蛋白将中和GBM的负电荷，并且将增强蛋白质渗透性。这将是蛋白质排泄的机制之一。少

The etiology of minimal change nephrotic syndrome(MCNS) is obscure. Several investigators have presumed that vascular permeability factor(VPF) derived from lymphocyte cultures in MCNS might be related to massive proteinuria. We already demonstrated that VPF was produced by T-lymphocytes from patients with MCNS. Furthermore, the infusion of T-lymphocyte culture supernatants from patients with MCNS into the left renal artery of rats, induced not only significant proteinuria in the rat urine but also a reduction of anionic sites in the glomerular basement membrane of the kidney in the hats. In order to determine the identity of T-lymphocyte subset in MCNS which release VPF, VPF assay of the culture supernatant of T-lymphocyte, CD4^+ cell or CD8^+ cell enriched fraction was performed. T-lymphocytes were purified by passage over a nylon wool column and separated to either CD4^+ cell or CD8^+ cell enriched fractions with monoclonal antibodies (anti-OKT4 and anti-OKT8 antibody) and a rabbit c … More omplement. VPF activity was found in either T-lymphocyte or CD4^+ cell enriched culture-supernatant. Moreover, its activity has not been inhibited by either anti-IL1 or anti-IL2 antibody. These results suggest that VPF might be different from lymphokines such as IL1 or IL2 and be produced by CD4^+ cells. Further studies are needed to clarify the correlations between VPF production of CD4^+ cells and massive proteinuria in MCNS.Next, it is reported that pI changes of serum and urine from nephrotic patients will be one of causes of protein excretion. We purified albumin from urine and investigated the pI and glomerul; basement membrane(GBM) permeability of rat kidney by infusing of the albumin. As the results, less anionic albumin was detected in the urine from MCNS patients. After infusion of the less anionic albumin to the rat kidney, the negative charge of the rat GBM was reduced and increased protein excretion. From these results, it is presumed that less anionic albumin will neutralized the negative charge of GBM, and will enhance the protein permeability. This will be one of the mechanism of protein excretion. Less