Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have proposed that the deposition in vivo of anti-brush border antibodies on proximal tubule cells in Heymann nephritis stimulates those cells to divide. To evaluate that hypothesis, we have investigated the temporal relationship between antibody deposition and kidney cell proliferation, using autoradiography to detect dividing cells in rats with Heymann nephritis and in age-matched controls treated with Freund's adjuvant alone. To assess the possible stimulation of proximal tubule cell proliferation by factors associated with proteinuria and/or nephrotic syndrome, kidney cell proliferation was measured in rats with chronic serum sickness glomerulonephritis. Proteinuric rats with chronic serum sickness also served as recipients of anti-brush border antibodies in passive transfer experiments. Cell division rates were not altered by adjuvant treatment or ageing. In both active Heymann nephritis and passive transfer experiments, a highly elevated stimulation of 3H-thymidine incorporation, reflecting mitotic activity, was detected in the proximal tubule epithelium immediately following the deposition of antibodies on the brush border. Significant enhancement of cell division was not noted in other nephron segments. A much smaller increase in proximal tubule cell proliferation accompanied proteinuria in chronic serum sickness. A similar small elevation compared to controls was also detected in late stages of Heymann nephritis when the proximal tubules were free of immunoglobulin deposits. It appears that the reaction of divalent antibodies with plasma membrane antigens can produce proliferative pathology of the proximal tubule epithelium. Furthermore, a significant, if less dramatic, enhancement of cell proliferation may be secondary to proteinuria and/or other manifestations of the nephrotic syndrome.
 ...
PMID:Antibody-mediated proliferation of proximal tubule cells. 325 99

Antibodies directed against tubular brush border antigens (RTE) are used to induce heterologous immune-complex nephritis. Among these antigens a glycoprotein with a molecular weight of 330 kilodaltons (gp330) has been shown to be of pathogenetic significance. We investigated whether antibodies other than those directed against gp330 are present in anti-RTE and whether they play a pathogenetic role. By using enzyme-linked immunosorbent assay techniques and Western blotting, we investigated polyclonal antibodies directed not only against crude RTE but also against RTEgp, a purified glycoprotein fraction of RTE, with respect to activity against glomerular basement membrane (GBM) components laminin, fibronectin, and type IV collagen. Both antibody preparations showed reactivity predominantly to the 220 kilodaltons subunit of laminin. Lower but nevertheless distinct reactivity to fibronectin and type IV collagen was also found. The antibody fraction directed against components of the GBM, which was isolated from anti-RTE IgG by affinity chromatography, showed linear binding to the GBM in indirect immunofluorescence studies. Injection of these antibodies into the renal artery also led to linear binding to the GBM with linear deposition of complement factors 3 and 9 and induced a weak and transient proteinuria. Immunoelectron microscopy revealed binding of the antibodies to glomerular epithelial and endothelial cell surfaces adjacent to the GBM. Injection of anti-RTE antibody absorbed to GBM components resulted in binding of antibodies and complement factors 3 and 9 in a fine granular pattern along the GBM, whereas injection of unabsorbed anti-RTE led to a course granular pattern. We conclude that the presence of antibodies (cross-)reacting with laminin, fibronectin, and type IV collagen in anti-RTE antibody has pathogenetic effects and could explain differences in pathogenicity between monospecific anti-gp330 antibody and polyclonal anti-RTE antibody.
 ...
PMID:Antibodies to purified renal tubular epithelial antigens contain activity against laminin, fibronectin, and type IV collagen. 327 61

Heymann nephritis (HN) is an experimentally induced glomerulonephropathy of the rat characterized by subepithelial immune deposits and proteinuria. Immunization with a complex multimeric glycoprotein, gp600, comprising four subunits gp330, gp140, gp110, and gp70 has been shown to induce the complete form of the disease including proteinuria. Examination of three different batches of heterologous anti-gp600 antisera by immunoblot technique showed that the reactivity toward gp70 was dominant and common to all three antisera. gp70 was isolated from Triton X-100-solubilized Fx1A by lectin Lens culinaris affinity chromatography, and the purity was confirmed by SDS-PAGE. Ten rats were actively immunized with 200 micrograms of gp70. All 10 animals developed circulating brush border antibody and typical granular IgG deposits in the glomerulus but only 1/10 animals developed abnormal proteinuria. A potent antiserum against gp70 was prepared in the rabbit. It reacted strongly to the glomerular capillary wall and the proximal tubular brush border by immunofluorescence. By Protein A immunogold technique using anti-gp70, gold particles were found associated with the glomerular basement membrane (GBM)-endothelial region. By immunoblot analysis of rat GBM using the same anti-gp70 antiserum, a 70-kDa cross-reactive antigen was demonstrated in GBM preparations. These results show that the smallest subunit, gp70 of the complete HN antigen, gp600/Fx1A can independently induce the lesion of HN, but without proteinuria. The presence of gp70 on the endothelial side of the GBM is consistent with a role for in situ antigen-antibody reactions at sites other than the subepithelial region in the pathogenesis of HN.
 ...
PMID:Nephritogenicity and immunocytochemical localization of the 70-kilodalton glycoprotein subunit (gp70) of Heymann antigen. 328 3

Passive Heymann nephritis (PHN) is an animal model of immune-complex-induced renal disease resembling human membranous glomerulonephritis. It was induced in rats by injecting rabbit antiserum directed against glycoprotein antigens isolated from rat embryonic visceral yolk-sac microvilli (VYS-MV). The glycoprotein antigens were isolated by extracting the VYS-MV with detergent Nonidet P-40 followed by gel filtration in Sephacryl S-300 and finally by lectin affinity chromatography with Ricinus communis agglutinin I. In vitro immunofluorescent localization studies demonstrated that the nephritogenic antibodies were localized along the apical region of the visceral yolk-sac endodermal cells and the brush border of the proximal tubular cells of the kidney. Rats injected with a single dose of the antiserum manifested proteinuria. Indirect immunofluorescent studies showed that the injected rabbit IgG was localized in vivo along the capillary walls of the glomerulus in a granular fashion. Electron microscopic examination of the same kidney glomeruli revealed numerous electron-dense deposits along the lamina rara externa of the glomerular basement membrane. Fusion of the epithelial foot processes was also present. These findings represent the typical immunopathological characteristics of Heymann nephritis. Furthermore, with the aid of Ouchterlony analysis, the antiserum against the isolated VYS antigens exhibited an immunoprecipitin band which was in common with that formed by the antiserum against the homogeneous nephritogenic antigen (gp330) of renal brush border origin. Thus, the nephritogenic antigens which have been found to be associated with the brush border of the renal proximal tubules may also be present or cross-reacted in the microvilli of the rat embryonic visceral yolk-sac.
 ...
PMID:Passive Heymann nephritis induced by rabbit antiserum to membrane antigens isolated from rat visceral yolk-sac microvilli. 330 94

We recently reported that an injection of antibody raised against renal brush border glycoprotein, gp108, in rats induced passive Heymann nephritis with acute and severe proteinuria. In this study, the distribution of gp108 in various rat tissues was investigated. On enzyme immunoassay, anti-gp108 antibody reacted to extracts of small intestine, lung, spleen, thymus, liver, epididymis, stomach, pancreas and heart. It also reacted to sera and extracts of peripheral blood cells, especially lymphocytes. These antigens, which are cross-reactive to kidney gp108 have similar biochemical properties: a molecular weight of about 108,000 and an isoelectric point of 4.8-5.4. These results show that immunologically and biochemically related antigens to renal glycoprotein, gp108, are present in various rat tissues.
 ...
PMID:The detection and characterization of renal brush border antigen (gp108) in various rat tissues. 330 35

Proximal tubule pathology in Heymann nephritis has been attributed to anti-brush border antibodies, but antibodies with other specificities might also be important. To determine whether injury to the basolateral membranes of proximal tubules could occur independently of brush border injury, LEW rats were immunized either with partially purified basolateral or brush border membrane vesicles. Both immunogens produced glomerular immunopathology and pathophysiology identical in magnitude and time course to that seen in Heymann nephritis. Antibodies eluted from the kidneys of rats immunized with either antigen preparation stained the brush border in vitro. However, circulating anti-brush border antibodies were in significant titers only in rats immunized with brush border vesicles, whereas antibodies that stained the cytoplasm of both proximal and distal tubules predominated in rats immunized with basolateral membranes. With the onset of proteinuria, rats immunized with brush border membranes developed the proximal tubule pathology of Heymann nephritis. In rats immunized with basolateral membranes, the brush border and apical aspect of proximal tubule cells remained essentially normal. However, defects of basolateral membrane transport function were present, indicating that those defects need not necessarily be secondary to brush border damage. The dissociation of brush border damage from glomerular injury suggests that different antibody populations may account for each. Furthermore, anti-brush border antibodies may not account for all aspects of proximal tubule pathology in Heymann nephritis.
 ...
PMID:Kidney immunopathology and pathophysiology in rats immunized with proximal tubule cell brush border or basolateral membrane vesicles. 331 82

The present study assessed the urinary protein with SDS-PAGE technique and by using gentamicin as a positive control for a comparative study to evaluate the renal toxic effect of gossypol. Results indicated that gentamicin could induce proteinuria by alteration of glomerular permeability to cause over-filtration of high molecular weight proteins, damage the brush border (BB) membrane of proximal renal tubules and impair tubular reabsorption function. Gossypol could also induce proteinuria in certain cases of guinea pigs but not at all in gossypol-treated rats. However, an increase in low molecular weight protein bands (M.W. range 20-30 kd) in urinary electrophoregram of gossypol-treated rats were detectable.
 ...
PMID:Evaluation of the renal tubulo-toxic effect of gossypol by urinary protein analysis with SDS-polyacrylamide gel electrophoresis. 337 Sep 89

To determine whether the induction of immune-mediated glomerular injury influences the formation of cyclooxygenase products by glomerular cells, we determined prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) (as the stable metabolite of TXA2) formation in isolated glomeruli of rats with passive Heymann nephritis (PHN). PHN is a model of membranous nephropathy mediated by antibody and complement independent of inflammatory cells. Five days following induction of PHN by injection of heterologous antibody to rat proximal tubular brush border antigen (Fx1A) rats developed proteinuria 36.5 +/- 34 (controls 3.8 +/- 1 mg/day). Treatment with cobra venom factor, which depleted complement C3 levels to less than 10% of baseline, prevented the development of proteinuria (6.9 +/- 2 mg/day). The development of subepithelial, glomerular immune-complex deposits and proteinuria was associated with a significant stimulation of glomerular PGE2 (87%) and TXB2 (183%) formation. This increment in glomerular prostanoid biosynthesis was significantly inhibited (PGE2 increased 22%, TXB2 increased 75%) in animals that were complement depleted with cobra venom factor. Cobra venom factor had no effect on glomerular prostanoid formation in normal rats. In additional experiments we tested the hypothesis that TXA2 may contribute to mediation of proteinuria in PHN. We utilized a thromboxane synthetase inhibitor UK38485. UK38485 reduced glomerular TXB2 formation by 80% without influencing glomerular deposition of 125I-labeled antibody, and did not alter levels of urine protein excretion in rats with PHN (control 42 +/- 21, UK 38485, 39 +/- 24 mg/day, P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Enhanced glomerular prostaglandin formation in experimental membranous nephropathy. 347 70

The distribution of the histochemical protein tracer, horseradish peroxidase, was studied in proximal tubules of rats with Heymann nephritis. Peroxidase reabsorption was substantially reduced in stage 2 of Heymann nephritis, a period during which the brush border of proximal tubules is severely damaged by specific antibodies. Impairment of the reabsorption function could not be attributed either to proteinuria or disturbances of proximal tubule metabolism and appeared to result from loss of microvilli. Recovery of brush border membrane morphology in stage 4 of Heymann nephritis was not accompanied by recovery of the normal capacity to reabsorb peroxidase. Functional deficits resulting from immunologic injury to proximal tubules in Heymann nephritis may persist despite waning of the anti-brush border antibody response and regeneration of the brush border of proximal tubule cells.
 ...
PMID:Reabsorption of horseradish peroxidase by proximal tubules in rats with Heymann nephritis. 348 9

Interstitial mononuclear cell infiltration in rats during the development of autoimmune Heymann nephritis (HN) was studied using the fine-needle aspiration biopsy (FNAB) technique. The results were compared with those obtained by immunohistochemical studies of infiltrating T helper (T-h) and T suppressor/cytotoxic (T-s) cells, and with traditional histopathological and immunofluorescence examinations. Three weeks after initial immunization with isolated tubular brush border antigen, when the histopathological finding was quite normal, FNAB revealed increased numbers of interstitial blast cells, large granular lymphocytes and activated lymphocytes. These increases reached significant levels 2 weeks after a booster injection and were still prominent in a few rats with manifest membranous glomerulonephritis (MGN) and proteinuria 14 weeks after initial immunization. Immunohistochemical staining 3 weeks after immunization showed a significant increase in T-h cells in peritubular regions. Infiltration decreased successively 2 weeks after the booster and during manifest MGN. On the other hand, the mean number of cortically infiltrating T-s cells successively increased during the course of the study and this increase had reached a statistically significant level 2 weeks after the booster. Prominent T-s infiltration appeared in a few rats 2 weeks after the booster and when MGN was histopathologically manifest, and it was then associated with histopathologically detectable interstitial mononuclear infiltration and also with blast cell infiltration in FNAB. Our results suggest linkage between tubulointerstitial lesions in HN and cell-mediated immunoreactivity, and that severe interstitial inflammation is associated with T-s cell infiltration. Cytological interpretation indicated that infiltrating blast cells were plasmablasts, which may imply local antibody production, especially since anti-brush border antibody titres and blast cell infiltration simultaneously reached maximum levels 2 weeks after the booster.
 ...
PMID:Interstitial mononuclear cell infiltration in Heymann nephritis. 350 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>