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)

Nephritis in rats was induced by intravenous injection of purified ferritin-conjugated rabbit and duck nephrotoxic globulin. Using the fluorescent antibody technique, the same capillary pattern was found as that in glomeruli of rats receiving uncoupled nephrotoxic globulin. Electron microscopy revealed a heavy accumulation of the basement membrane-fixed antibody almost exclusively at the endothelial side. A higher concentration of ferritin was demonstrable in the peripheral basement membrane. The once-fixed antibody remained at the site of reaction though decreasing with time. The half-disappearance time seemed to be shorter than that of the uncoupled nephrotoxic globulin. No difference in localization was observed between rabbit and duck antibody. At least 40 basement membrane-fixed antibody molecules from the rabbit per 3000 mmicro(2) of filtration surface were needed to cause immediate nephritis. To induce nephritis using duck antibody, a greater number of basement membrane-fixed antibody seemed to be necessary. No evidence of specific reaction with constituents of glomerular cells was obtained.
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PMID:Electron microscopic localization of the nephrotoxic antibody in the glomeruli of the rat after intravenous application of purified nephritogenic antibody-ferritin conjugates. 487 69

In the experimental tubulo-interstitial (anti-basement membrane) nephritis in the rat, electron microscopic studies after the in vivo microinjection of native ferritin in areas of granulomatous inflammation near the surface of the kidney indicate that epitheloid and multinucleate Langhans' giant cells are capable of endocytosis and particularly of micropinocytosis. This suggests the possibility that endocytotic activities as well as secretion phenomena are important in the immune defense mechanisms linked with these "specifically" developed cells.
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PMID:Endocytotic activity in epitheloid and Langhans' giant cells. Tracer studies with ferritin in the tubulointerstitial (anti-TBM) nephritis model. 615 Dec 98

A method is described for performing postembedding staining of protein (immunoglobulin) antigen embedded in styrene-methacrylate resin. Fixation of specimens in a combination of 4% paraformaldehyde and 0.2% picric acid and washing in buffer containing 7% sucrose, followed by abrupt dehydration with absolute acetone in the cold preserved the antigenicity, although in a masked form. The masked antigenicity could be reexposed by treatment with nonspecific protease. Staining with fluorescent-, peroxidase-, or ferritin-labeled antibodies on semi- and ultrathin sections resulted in specific localization of the antigen. We applied this technique to the localization of rabbit immunoglobulin in specimens of renal tissue obtained from rats with anti-glomerular basement membrane nephritis; we also localized human IgG in a renal biopsy specimen. The prerequisites for recovery of antigenicity are such that preservation of tissue structure at the light microscopic level is good, but relatively poor at the electron microscopic level.
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PMID:An approach to postembedding staining of protein (immunoglobulin) antigen embedded in plastic: prerequisites and limitations. 615 34

Immunologic mechanisms of proteinuria and ultrastructural alterations of the slit pore complex and glomerular charge barrier were investigated in Munich Wistar (MW) rats with nephrotoxic serum nephritis. Prior to disease induction, normal MW sera demonstrated 50% of the complement hemolytic activity compared with sera obtained from Sprague-Dawley rats. MW rats were sacrificed prior to, at onset (5 to 6 hours), and during maximal proteinuria (heterologous phase). Immunofluorescence revealed binding of rabbit antirat IgG antibodies in a linear pattern to the glomerular basement membrane (GBM) within 15 minutes postinjection. Complement deposition was not demonstrable in vivo in this model. Immediately after injection of nephrotoxic serum a decreased penetration of the GBM occurred, restricting ferritin to the level of the endothelium in in situ fixed glomeruli. GBM permeability to native ferritin did not increase despite areas of epithelial cell detachment, endothelial cell sloughing, and proteinuria between 2 and 24 hours postnephrotoxic serum injection. Colloidal iron initially decreased staining intensity between 6 and 8 hours, with a major decrease at 24 hours, indicating a loss in glomerular sialoprotein coincident with the onset of proteinuria. Polyethyleneimine (PEI) localization revealed an initial loss of anionic binding sites by 2 hours postinjection. At 6 hours peripheral capillary loops demonstrated only scattered, random polyethyleneimine-binding sites. Splitting of the lamina densa occurred at 24 hours with the exposure of previously undetected anionic binding sites within the lamina densa. Ultrastructurally, as early as 2 hours postnephrotoxic serum injection tissue perfused with tannic acid-glutaraldehyde showed epithelial membranes forming numerous pinocytotic vesicles. Blunting and retraction of foot processes caused displacement and stacking of slit diaphragms prior to the onset of proteinuria. Between 6 and 24 hours postinjection, slit diaphragms appeared to stretch and contract to compensate for epithelial cell retraction. Tangential sections showed neither alterations nor condensation products disrupting the isoporous substructure of the slit diaphragm 24 hours postnephrotoxic serum injection. Polymorphonuclear leukocytes were not found within capillary loops during the heterologous phase of nephrotoxic serum nephritis in MW rats. The absence of complement and polymorphonuclear leukocytes accompanying anti-GBM antibody deposition suggests that early epithelial cell injury and GBM charge alterations in MW rats are mediated by heterologous antibody via a complement-independent mechanism. The lower complement hemolytic activity in normal MW sera may explain the lack of complement involvement in renal lesions in this model of nephrotoxic serum nephritis. Loss of characteristic staining for both glomerular sialoprotein and discrete anionic sites in the GBM coincided with early epithelial cell alterations and occurred prior to the onset of measurable proteinuria.
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PMID:Complement-independent nephrotoxic serum nephritis in Munich Wistar rats. Immunologic and ultrastructural studies. 634 11

The uptake and transport of immune complexes (IC) in glomeruli were studied in Arthus-type nephritis induced by ferritin anti-ferritin IC. This experimental nephritis was transient in nature, forming electron dense aggregates and deposits in glomeruli, and was considered to be suitable for the analysis of the glomerular defence against immune complex injury. The IC were taken up and removed from the glomerular circulation first by polymorphonuclear leukocytes and later by macrophages. The IC in the glomerular capillary walls and mesangium were seen to shift slowly from the peripheral part of the glomeruli to the more central and juxtaglomerular area. It is speculated that the glomerular integrity is maintained from the immune complex induced tissue injury through the handling and removal of phlogogenic IC by the blood derived phagocytic system and intrinsic glomerular clearing system.
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PMID:Arthus-type nephritis. II. Glomerular clearing system against poorly soluble and insoluble immune complexes. 645 2

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

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

A study was performed to elucidate the mechanisms of charge-based immune complex nephritis. A chronological observation after induction of nephritis was made by immunoelectron microscopy to clarify whether antigen (Ag) remains in association with antibody (Ab) and C3 during the translocation through the glomerular basement membrane (GBM). Fifteen minutes after intrarenal perfusion with cationized ferritin (pI > 10.0) as Ag, followed by injection of rabbit anti-ferritin Ab, deposition of subendothelial Ag-Ab-C3 complexes was observed. Between 2 hours and 1 day, a large number of Ag in close association with Ab was noted in the lamina densa, but only a small amount of C3 was detectable. During this time Ag and Ab in the subendothelial region gradually decreased. However, C3 reappeared in the subepithelial region together with the Ag-Ab complex after 1 day, and the subendothelial C3 significantly decreased. At 2 hours and day 1, the distributions of Ag and Ab in the GBM were similar in immersion-fixed kidneys regardless of the preperfusion with phosphate-buffered saline. On the other hand, the passage of Ag across the lamina densa was delayed in the experimental rats as compared with the controls. Significant albuminuria also appeared on day 1. Despite the general concept that Ab binding to cationized Ag results in low avidity immune complex, cationized Ag translocated across the GBM in close association with Ab. The complement was activated biphasically in the subendothelial and in the subepithelial space. The subendothelial complement activation may have contributed to the translocation of immune complex.
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PMID:Intraglomerular basement membrane translocation of immune complex (IC) in the development of passive in situ IC nephritis of rats. 845 43

Familial juvenile nephronophthisis (NPH) is a hereditary form of chronic tubulointerstitial nephritis with onset in childhood. About one-third of patients develop anaemia before renal insufficiency. We investigated the pathogenetic mechanisms leading to anaemia by comparing 6 patients with NPH and 12 reference patients with other renal diseases. We studied their iron metabolism and measured transferrin receptor-ferritin ratios. There was no evidence for iron deficiency or haemolysis. The serum erythropoietin concentrations of the patients with NPH (12 +/- 2.3 U/I) were low compared with the 12 reference patients (25 +/- 18.9 U/I). In the 2 patients with NPH who were fully investigated, the pharmacokinetics of recombinant human erythropoietin appeared normal. Thus, anaemia in patients with NPH does not result from iron deficiency or correlate with impaired iron status. The mechanism underlying the anaemia of NPH appears to affect the function or regulation of the cells producing erythropoietin.
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PMID:Mechanism underlying early anaemia in children with familial juvenile nephronophthisis. 889 59


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