Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The charge-based barrier of the glomerular capillary filter was investigated in normal mice and in mice with immune complex lupus nephritis. Cationized ferritin (CF), pI 7.7 To 8.5, was used as a molecular probe of fixed anionic sites. Mice with various degrees of proteinuria and severity of glomerulonephritis were systemically injected with CF and their glomeruli studied ultrastructurally employing morphometric methods. A decreased and erratic localization of CF was observed in the lamina rara externa, in the intervening basement membrane between immune deposits, and in basement membrane projections, areas previously shown to be abnormally permeably to a large anionic protein. In small numbers, CF molecules were found in residual epithelial slits and in the urinary space. In normal mice, CF regularly labeled the laminae rarae of the glomerular basement membrane and the slit pore area but not leak into the urinary space. Such differences in CF localization in capillary loops of proteinuric and normal mice were confirmed by morphometric estimate of particle counts. Focal areas of increased permeability to anionic protein are deficient of and/or exhibit a disorderly redistribution of fixed anionic sites.
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PMID:Glomerular permeability: focal loss of anionic sites in glomeruli of proteinuric mice with lupus nephritis. 644 31

To verify whether an increase in glomerular permeability precedes the deposition of immune complexes in the capillary wall, the following were studied in mice with lupus nephritis: 1) urinary proteins; 2) glomerular transfer of IgG, albumin, and anionic ferritin (AF) (isoelectric point, 4.2-4.6); and 3) anionic groups of the capillary wall as detected by binding of cationized ferritin (CF) (isoelectric point, 7.5-8.6). The glomeruli were investigated by immunofluorescence, immunoelectron, and transmission electron-microscopic studies. Urinary proteins were quantitated and characterized by electrophoresis. When mice were 5 months of age, (the time at which pathologic proteinuria was first detected), immune deposits were few and were confined to the mesangium. Although AF molecules were largely retained at the level of the lamina rara interna, focal leakage of albumin and IgG was detected across capillary walls that were not found to contain immune deposits. Focal and irregular loss of anionic groups, reflected by decreased binding of CF molecules, occurred in the laminae rarae of the basement membrane. Foot processes of glomeruli incubated with CF showed no loss of polyanion. We conclude that the increase in glomerular permeability that precedes deposition of immune complexes is due, in part, to focal loss of anionic groups of the basement membrane.
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PMID:Decreased anionic groups and increased permeability precedes deposition of immune complexes in the glomerular capillary wall. 645 33

To examine the effect of T lymphocyte deficiency on the course of immune complex nephritis, we studied renal function and structure in Swiss albino nude and non-nude mice following injection of heterologous protein. Four groups of 22 mice each (two nude and two non-nude) received either apoferritin 2 mg or saline daily for 10 weeks. Nude mice were maintained in a gnotobiotic environment. Non-nude mice receiving apoferritin developed proteinuria and had increased cellularity within glomeruli compared to either nude mice receiving apoferritin or to control groups (p less than 0.05). Of 22 non-nude mice receiving apoferritin, 16 had glomerular immune deposits by electron and immunofluorescent microscopy while 9 of 22 counterpart nude mice receiving apoferritin had such deposits. Non-nude mice more commonly showed membraneous deposits. Nude and non-nude mice receiving saline had no glomerular deposits. These preliminary data suggest that T lymphocytes may play a significant role in the development of immune complex nephritis.
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PMID:Immune complex nephritis in nude mice. 646 Jan 98

The glomerular lesions of focal sclerosis clinically associated with a steroid-resistant nephrotic syndrome, are of unknown origin. IgM and C3 deposits and electron dense material found in areas of sclerosis are not convincing evidence of an immune pathogenesis. These deposits have been studied in a rat model of focal sclerosis induced by uninephrectomy and repeated aminonucleoside administration. Sclerotic lesions closely resembling human disease developed in the remaining kidney. There was a severe progressive proteinuria. Seventy-eight days after initial aminonucleoside injection 65 per cent of glomeruli were sclerotic with IgM, IgG, C3 and fibrinogen deposits, and electron dense deposits by electron microscopy. To study macromolecule in this model of focal sclerosis, ferritin uptake 4 and 24 h after intravenous ferritin given at 77 days was compared in focal sclerosis rats with control rats without sclerosis (uninephrectomy plus saline-only injections). In focal sclerosis rats sclerotic areas contained massive accumulations of ferritin. In unaffected segments of sclerotic glomeruli, and normal glomeruli of focal sclerosis rats, ferritin concentration was no different from controls. Abnormal ferritin trapping in areas of sclerosis suggests that the presence of IgM and C3 may be due to a similar mechanism, and is not indicative of an immune pathogenesis for focal sclerosis.
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PMID:Ferritin deposition in the glomerular deposits of focal glomerular sclerosis in the rat. 648 27

A model of immune complex glomerulonephritis (ICGN) produced in mice by the daily injection of apoferritin was employed to study the effect of treatment with various doses of prostaglandin E2 (PGE2) on glomerular damage, immune complex deposition, proteinuria, and serum anti-apoferritin antibody. Administration of PGE2, 200 micrograms twice daily, resulted in a significant decrease in glomerular damage and immune complex deposition, prevented the development of proteinuria, and significantly reduced serum levels of anti-apoferritin antibody. PGE2, 100 micrograms twice daily, resulted in a decrease in immune complex deposition as assessed by immunofluorescence microscopy, but this dosage did not significantly alter glomerular damage, proteinuria, or antibody levels. PGE2 dosages of 50 and 25 micrograms twice daily had no effect on any of these parameters. The protective effect of PGE2 on the development of ICGN occurred only at dosages that were associated with decreased anti-apoferritin antibody.
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PMID:Treatment of murine immune complex glomerulonephritis with prostaglandin E2: dose--response of immune complex deposition, antibody synthesis, and glomerular damage. 657 81

In the present study in Munich-Wistar rats during the initial stages of autologous immune complex nephritis (protein excretion 3 to 50 mg/24 hours) we examined the sequential changes in binding of cationized ferritin to anionic sites, as well as alterations in staining with colloidal iron of podocyte membrane sialoglycoprotein and correlated these with changes in glomerular basement membrane permeability to native ferritin. The results are compared with those obtained from rats with advanced autologous immune complex nephritis (protein excretion 100 to 350 mg/24 hours) and with normal control rats. The formation of the smallest detectable immune complex deposits was associated with a concomitant decrease in binding of cationized ferritin to anionic sites in the lamina rara externa in the area of the deposits. This was accompanied by a diminution in staining by colloidal iron of the epithelial cell coat overlying the deposits. The staining of the remainder of the epithelial cell glycocalyx, however, remained unaltered even in the presence of severe proteinuria. Alterations in the permeability of the glomerular basement membrane to native ferritin could not be documented until protein excretion exceeded 10 mg/24 hours. The gradual loss of staining of the epithelial cell glycocalyx adjacent to immune complexes supports the concept that, as immune complexes are formed in situ by the interaction of antibodies with a glycoprotein present on the epithelial cell surface, they are shed and gradually accumulate in the lamina rara externa. Furthermore, as the immune complex deposits enlarge they destroy and/or mask the heparan sulfate anionic sites in the lamina rara externa resulting in a decreased number of anionic binding sites for cationized ferritin.
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PMID:Alterations in glomerular anionic sites in autologous immune complex nephritis. 662 Sep 83

We investigated the effects of methylprednisolone on the glomerular permeability of mice with lupus nephritis. At the onset of nephritis, the mice were divided into two groups: one group was injected with methylprednisolone and the other with saline; treatment continued for 12 weeks. We determined the protein concentration in specimens of urine collected every 2 weeks, and pre- and posttherapy urine samples were analyzed by electrophoresis. After 12 weeks, we injected anionic or cationized ferritin systemically into mice of each group and studied kidney samples by electron microscopy. At the onset of nephritis (5 months of age), proteinuria (5.2 mg/day) was selective and albumin was the predominant (87%) protein excreted. Electron-dense deposits were then confined to mesangial areas. In untreated mice, protein excretion values doubled at 5.5 months of age, tripled at 6 months of age, and increased 5-, 7-, 9-, and 11-fold at subsequent intervals of 2 weeks, to reach 55.0 mg/day at 8 months of age. Proteinuria was poorly selective, and protein excretion values correlated inversely with survival rate (35% at the end of study). The glomerular basement membranes were studded with electron-dense deposits and were depleted in anionic sites, as judged by decreased binding of cationized ferritin molecules. The anionic ferritin molecules permeated the basement membrane at the vicinity of electron-dense deposits and reached the urinary space through residual slit pores. In methylprednisolone-treated mice, by contrast, protein excretion values were low, proteinuria was selective, and remained virtually unchanged at 5.3 mg/day by 8 months of age. There were no deaths in this group. Most of the electron-dense deposits were present in mesangia. Anionic sites of the glomerular basement membranes were largely preserved and anionic ferritin molecules were mostly limited to the luminal aspect of the basement membrane. These studies suggest that methylprednisolone therapy preserved glomerular permeability characteristics by decreasing the localization of immunoreactants in glomeruli and by interfering with factors that favor the localization of immune complexes in the capillary wall.
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PMID:Murine lupus nephritis. Effects of glucocorticoid on glomerular permeability. 670 52

Forty-three spinal cord injured patients with endstage renal disease (ESRD) maintained on hemodialysis were studied. The most prevalent renal lesions consisted of chronic pyelonephritis and amyloidosis while the main renal functional features included nephrotic range proteinuria, high urine output and relatively low serum creatinine for the degree of renal insufficiency. Normocytic, normochromic anemia with low reticulocyte response, low serum iron and iron binding capacity and high transfusion requirement and serum ferritin were noted. Various cardiovascular, pulmonary and gastrointestinal abnormalities were found with considerable frequencies. The incidence of amyloidosis was much higher than that reported previously. This is thought to be due to continued progression of amyloidosis occasioned by longer survival in the present series.
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PMID:Clinicopathological characteristics of dialysis patients with spinal cord injury. 688 88

Rabbits given a single intravenous injection of highly cationised horse spleen ferritin (isoelectric point greater than 9.5), 2 to 100 mg/kg of body weight, frequently developed glomerulonephritis, and a substantial proportion became nephrotic. The disease usually remitted spontaneously. Renal tissue obtained before onset of proteinuria (by biopsy), during the acute phase and in the phase of remission, was examined for the presence of cationized ferritin, rabbit IgG, and C3 by immunofluorescence. Electron microscopy was performed on material prepared conventionally and after treatment with polyethyleneimine (to visualize fixed anionic sites in the glomeruli). Cationic ferritin molecules initially bound to the fixed anionic sites in the glomerular basement membrane but disappeared before the onset of proteinuria (6 +/- 3 days). Glomerular deposition of rabbit immunoglobulin or complement was not seen, and electron microscopy did not reveal deposits in the glomerular capillary walls. This makes it unlikely that immune complexes play a role in the pathogenesis of the induced disease. The striking features were extensive loss of epithelial foot processes and pronounced loss of negative charge from the glomerular basement membrane and from the epithelial cell surface coat. These changes preceded onset of proteinuria and, by reference to those animals not developing proteinuria, were seen to be closely linked to the subsequent development of proteinuria. It appears that the transient interaction of a cationic, macromolecular protein antigen with the fixed anionic sites in the glomerular basement membrane can set a chain of events in motion that leads to loss of negative charge and epithelial cell withdrawal, ultimately resulting in proteinuria.
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PMID:Cationic macromolecule-induced nephrotic syndrome in rabbits. Lack of immune complex involvement. 688 83

We studied the effect of PGE1 in pharmacologic doses on immune complex-induced glomerulonephritis produced by daily intraperitoneal injections of apoferritin. Mice received one of the following injection schedules: apoferritin 4 mg/day, apoferritin 4 mg/day plus PGE1 200 microgram twice daily, saline, or PGE1 200 microgram twice daily. Administration of apoferritin alone resulted in mesangial cell proliferation in all 14 mice with crescent formation in nine. Evidence of subepithelial and mesangial immune complex deposition and a significant increase in urine protein excretion was found. Treatment with PGE1 resulted in a mild increase in mesangial cells in six of 14 mice. No mice developed crescents on this regimen. In addition, proteinuria was prevented, and there was a marked diminution of immune complex deposition. Antiapoferritin antibody was detected in the sera of mice from both groups. No alteration in lymphocyte response to mitogen or in vitro PGE1 suppression of blastogenesis was detected. Our results indicate that PGE1 therapy alters immune complex glomerulonephritis in this model of murine chronic serum sickness by reducing glomerular immune complex deposition. However, no difference in specific or nonspecific immunologic responses was detected.
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PMID:Prostaglandin E1 therapy of murine chronic serum sickness. 699 40


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