Increase in Proteinuria and Reduction in Number of Anionic Sites on the Glomerular Basement Membrane in Rabbits by Infusion of Human Nephrotic Plasma <i>in Vivo</i>

Ah, Wilkinson; Gillespie, Cathleen; Hartley, B; Dg, Williams

doi:10.1042/cs0770043

Cited by 25 publications

(11 citation statements)

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“…The contribution of agrin may be crucial regarding its homogeneous presence in the GBM ( Figure 3) and its abundance in isolated glomeruli (Table 2). Hence, agrin could be essential to maintain charge selectivity during ultrafiltration (Kanwar et al 1991;Vernier et al 1992;Wilkinson et al 1989). …”

Section: Discussionmentioning

confidence: 99%

Agrin Is a Major Heparan Sulfate Proteoglycan in the Human Glomerular Basement Membrane

Groffen

Rüegg

Dijkman

et al. 1998

J Histochem Cytochem.

155

100

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Agrin is a heparan sulfate proteoglycan (HSPG) that is highly concentrated in the synaptic basal lamina at the neuromuscular junction (NMJ). Agrin-like immunoreactivity is also detected outside the NMJ. Here we show that agrin is a major HSPG component of the human glomerular basement membrane (GBM). This is in addition to perlecan, a previously characterized HSPG of basement membranes. Antibodies against agrin and against an unidentified GBM HSPG produced a strong staining of the GBM and the NMJ, different from that observed with anti-perlecan antibodies. In addition, anti-agrin antisera recognized purified GBM HSPG and competed with an anti-GBM HSPG monoclonal antibody in ELISA. Furthermore, both antibodies recognized a molecule that migrated in SDS-PAGE as a smear and had a molecular mass of approximately 200-210 kD after deglycosylation. In immunoelectron microscopy, agrin showed a linear distribution along the GBM and was present throughout the width of the GBM. This was again different from perlecan, which was exclusively present on the endothelial side of the GBM and was distributed in a nonlinear manner. Quantitative ELISA showed that, compared with perlecan, the agrin-like GBM HSPG showed a sixfold higher molarity in crude glomerular extract. These results show that agrin is a major component of the GBM, indicating that it may play a role in renal ultrafiltration and cell matrix interaction. (J Histochem Cytochem 46:19-27, 1998)

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Section: Discussionmentioning

confidence: 99%

Agrin Is a Major Heparan Sulfate Proteoglycan in the Human Glomerular Basement Membrane

Groffen

Rüegg

Dijkman

et al. 1998

J Histochem Cytochem.

155

100

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“…In rats, serum factors [14,15] and supernatants from IMLNS PBMC cultures [16,17], when injected into the renal artery, have been shown to induce albuminuria [14,16,17] and to decrease the GBM anionic sites [15][16][17]. We reported that serum interleukin-8 (IL-8) levels are increased in IMLNS patients in relapse.…”

Section: Discussionmentioning

confidence: 96%

The effect of lymphocytes from renal transplant patients on glomerular basement membrane sulfate uptake

Garin

Self

1995

Pediatr Nephrol

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We have studied the effect of peripheral blood mononuclear cells (PBMC) from renal transplant patients on 35sulfate uptake by rat glomerular basement membrane (GBM). Nine patients were included in the study; six were studied during an episode of acute allograft rejection and seven while not undergoing acute rejection. The sulfate uptake index, calculated as the ratio between uptake by GBM from rat glomeruli cocultured with PBMC and 35sulfate incorporation by GBM from glomeruli cultured alone, was significantly higher when glomeruli were cocultured with PBMC from patients undergoing an acute rejection (3.26 +/- 1.18, mean +/- SEM) than it when glomeruli were cocultured with PBMC from nonrejecting transplant patients not showing proteinuria (0.81 +/- 0.11) (P = 0.0053). After reversing the acute allograft rejection with resolution of proteinuria, the sulfate uptake index returned to normal in four of five patients. The fifth patient had persistent nephrotic syndrome and his sulfate uptake index remained elevated. These findings are similar to those observed in idiopathic minimal lesion nephrotic syndrome patients in relapse. Because the GBM sulfated compounds may play a role in glomerular permeability to plasma proteins, by acting on these compounds PBMC may be a common mechanism for proteinuria.

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“…Several studies have demonstrated increased urinary protein excretion after infusion into the rat circulation of plasma or serum from patients with IMLNS as well as supernatant from IMLNS PBMC cultures [9,10,11,12,13,14]. Previous studies reported injecting the tested substance into the rat circulation in vivo using a comparatively large fluid volume within a short period of time (usually less than 1 h).…”

Section: Discussionmentioning

confidence: 99%

“…Experimental data showing the induction of proteinuria in rats upon the injection of supernatants from PBMC cultures from IMLNS patients in relapse, plasma or serum of the same patients, or a factor produced by human T cell hybridoma have supported the hypothesis of a circulating factor causing proteinuria in IMLNS [9,10,11,12,13,14,15]. We have conducted experiments showing that a cytokine secreted by PBMC from patients with IMLNS in relapse induced proteinuria in rats after 5 days of continuous intrarenal arterial infusion [9].…”

Section: Introductionmentioning

confidence: 99%

Proteinuria and Fusion of Podocyte Foot Processes in Rats after Infusion of Cytokine from Patients with Idiopathic Minimal Lesion Nephrotic Syndrome

Garin

Laflam²,

Muffly³

2005

Nephron Exp Nephrol

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Background/Aims: We report on the isolation of a factor secreted by peripheral blood mononuclear cells from patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) in relapse and its effect on proteinuria and podocyte morphology in the rat. Methods: Peripheral blood mononuclear cells from patients with IMLNS (in relapse and in remission) and patients with focal segmental glomerulosclerosis were cultured for 72 h. Supernatants from 20 × 10⁶ cultured cells were separated by liquid chromatography into three fractions according to markers (bovine serum albumin, β-amylase, and apoferritin). Each supernatant fraction was infused into rats for 5 days using an osmotic pump. Proteinuria, 24-hour albumin excretion or albumin/creatinine ratio in a 24-hour urine collection, was measured daily starting 3 days prior to fraction infusion. Renal tissue was obtained for electron microscopy studies. The β-amylase fraction underwent electrophoresis using isoelectric focusing gel. Results: When protein excretion was compared prior to and during supernatant fraction infusion, a significant increase in proteinuria was observed only when β-amylase fraction from IMLNS patients in relapse was infused (p < 0.05). Protein electrophoresis of the β-amylase fraction showed a single band at pH 6.0 only in samples from IMLNS patients in relapse. The band was composed of two proteins, β-amylase and a 100-kDa glycoprotein. Fusion of foot processes was observed only when the β-amylase fraction from IMLNS patients in relapse was infused. Conclusions: The infusion of the β-amylase fraction containing a 100-kDa glycoprotein from IMLNS patients in relapse induced proteinuria and effacement of foot processes in the rat. This protein may play a role in the pathogenesis of IMLNS.

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Increase in Proteinuria and Reduction in Number of Anionic Sites on the Glomerular Basement Membrane in Rabbits by Infusion of Human Nephrotic Plasma in Vivo

Cited by 25 publications

References 0 publications

Agrin Is a Major Heparan Sulfate Proteoglycan in the Human Glomerular Basement Membrane

Agrin Is a Major Heparan Sulfate Proteoglycan in the Human Glomerular Basement Membrane

The effect of lymphocytes from renal transplant patients on glomerular basement membrane sulfate uptake

Proteinuria and Fusion of Podocyte Foot Processes in Rats after Infusion of Cytokine from Patients with Idiopathic Minimal Lesion Nephrotic Syndrome

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