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)

We employed a model of immune complex glomerulonephritis produced in mice by the daily injection of apoferritin to study the effect of treatment with arachidonic acid (AA). Apoferritin injections produced demonstrable glomerular damage by light microscopy associated with deposition of immunoglobulin along peripheral capillary loops. Treatment with AA 100 micrograms daily resulted in significantly less glomerular damage and a shift inthe location of immune complex deposition to the mesangium. The amount of anti-apoferritin antibody was determined by hemagglutination and found to be significantly decreased in mice treated with AA. Separate studies employing this dose of AA revealed that the number of IgM antibody producing cells to SRBC was not altered by AA.
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PMID:Alteration in immune complex glomerulonephritis by arachidonic acid. 680 91

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

In the model described here the ability of cationized (basic) ferritin to bind to the glomerular basement membrane and act as a planted antigen was exploited. This planted antigen was accessible to circulating antibody resulting in in situ immune complex formation. Perfusion of cationized ferritin (isoelectric point greater than 9.5) directly into the renal arteries, followed by intravenous injection of anti-ferritin antibody resulted in induction of glomerulonephritis with heavy proteinuria lasting for about 3 weeks. Fine granular deposition of antigen, antibody and rat C3 along the glomerular capillary walls was seen by immunofluorescence. Electron microscopy revealed the presence of subepithelial deposits containing ferritin; the foot processes were fused. This demonstrates the potential role of basic antigens in the pathogenesis of in situ immune complex glomerulonephritis.
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PMID:A model of in situ immune complex glomerulonephritis in the rat employing cationized ferritin. 701 52

A nine-year-old girl was hospitalized because of hypoxemia and anemia. Antibasement-membrane antibodies were present in the serum, but there was no renal involvement suggestive of Goodpasture's glomerulonephritis. Biopsy of the lung showed pulmonary hemosiderosis. In ultrastructural analysis, no lesion of the alveolar basement membrane or capillary endothelial cells was found; however, ferritin-looking deposits were present on alveolar basement membranes and the elastic lamina of arterioles and venules. Mineralogic studies showed these deposits to be made of iron and calcium (this latter element was probably precipitated on altered basement membranes or elastic lamina). Hemosiderin inclusions in the macrophages contained iron but no detectable calcium.
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PMID:Idiopathic pulmonary hemorrhage. Ultrastructural and mineralogic study. 705 32

The mesangial egress, but not the uptake of radiolabeled aggregated human immunoglobulin G (AHIgG125I) (macromolecular proteins biologically akin to immune complexes), deviated markedly from normal in rats with preexisting ferritin-antiferritin immune complexes in the mesangium. Sprague-Dawley rats, given daily intraperitoneal ferritin, 8 mg. per 100 gm. of body weight, for 6 weeks (Ferritin rats), uniformly developed intense mesangial staining for IgG and C3 by immunofluorescence microscopy but minimal glomerular proliferation by light microscopy. With electron microscopy, ferritin was seen in mesangial channels and also in mesangial cells. These rats had normal serum creatinine, no hematuria or proteinuria. AHIgG125I, 50 mg. per 100 gm of body weight, was given intravenously to control and to Ferritin rats; groups of five control and five Ferritin rats were sacrificed at 2, 4, 8, 16, and 24 hours after injection. AHIgG125I was measured in preparations of isolated glomeruli and compared with simultaneous spleen, liver, and blood levels. At all time intervals, blood levels of > 7 S AHIgG125I were similar in control and Ferritin rats. Initial, 2-hour mesangial uptake of AHIgG125I was similar in control and Ferritin rats. During the 2- to 16-hour interval, the disappearance of AHIgG125I from glomeruli of Ferritin rats was delayed; glomerular AHIgG125I concentration decreased 85 per cent in control but only 38 per cent in Ferritin rats. After the administration of AHIgG125I, hematuria (2 to 3+) developed in 60 per cent of Ferritin rats but not in control rats. These studies suggest that immune complexes of different antigen-antibody systems may influence the kinetics of each other locally, at the glomerular level. This impaired mesangial clearance of immune complexes may favor the development of glomerular injury. The experimental model described may be relevant to some forms of human glomerulonephritis in which mesangial pathology and immunopathology are characteristic, and may explain some of the pathogenetic mechanisms operative in these diseases in man.
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PMID:Impaired mesangial clearance of macromolecules in rats with chronic mesangial ferritin-antiferritin immune complex deposition. 744 26

The resolution phase of inflammation is being increasingly recognized as a dynamic multifaceted process whose components may be amenable to pharmacological manipulation for therapeutic gain. Here, we review evidence that the lipoxins (LX), a family of lipoxygenase-derived eicosanoids generated during cell-cell interactions within the vascular lumen, are potential endogenous inhibitors of polymorphonuclear neutrophil (PMN) recruitment during glomerular inflammation. LX are generated in nanogram quantities in kidneys of rats with Concanavalin A-ferritin (Con A-F) immune complex glomerulonephritis and of mice with acute nephrotoxic serum nephritis (NSN). PMN-platelet transcellular pathways appear to be the major route to LX formation in these settings, PMN donating the labile epoxide intermediate leukotriene A4 for conversion by platelet LX synthase to LXA4. Complementary approaches using monoclonal antibodies and gene knockout suggest that PMN-platelet adhesion through P-selectin promotes transcellular LXA4 biosynthesis in vitro and in vivo. In support of a modulatory role in PMN trafficking; LXA4 and LXB4, the LX generated in greatest quantities by mammalian cells, inhibit PMN chemotaxis, adhesion to endothelial cells, and migration across endothelium and epithelium induced leukotrienes and some other mediators in vitro. Exposure of PMN to LXA4 ex vivo attenuates their recruitment in Con A-F glomerulonephritis. Furthermore, PMN recruitment is exaggerated during NSN in P-selectin knockout mice, coincident with reduced efficiency of transcellular LXA4 generation and reduced renal LXA4 levels. Replenishment of platelet P-selectin by transfusion of null mice with wild-type platelets reverses this defect in LXA4 synthesis and approximates PMN infiltrates in null and wild-type animals. Against this background, LXA4 stable analogues have been designed that retain the biologic activity of native LXA4 in vitro and should be useful tools for probing the therapeutic potential of LXA4 in disease. In the presence of aspirin, endothelial cell cyclooxygenase II (COX-II) transforms arachidonic acid to 15R-hydroxyeicosatetraenoic acid which, in the context of PMN-endothelial cell interaction, is converted by PMN 5-lipoxygenase to 15-epi-LX. Intriguingly, these novel LX also attenuate PMN adhesion and transmigration in model in vitro systems. Together, these observations suggest that LX may not only play important regulatory roles in the "stop programs" of renal inflammation, but also contribute to the anti-inflammatory activity of aspirin and related inhibitors of COX-II.
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PMID:Lipoxins, leukocyte recruitment and the resolution phase of acute glomerulonephritis. 906 45

The ultrastructural localization of immune complex (IC) and inflammatory mediator systems in the glomerulus was investigated in active in situ IC glomerulonephritis employing cationized ferritin in rats. Glomerulonephritis was induced by unilateral renal perfusion of cationized ferritin as antigen (Ag) in preimmunized rats, and anti-ferritin antibody (Ab), C3 and the rat C5b-9 complex were localized by means of immunogold electron microscopy. Ag-Ab complexes were initially formed subendothelially, associated with C3, and attracted platelets, polymorphonuclear leucocytes (PMN) and monocytes. Then Ag-Ab complexes, without C3, passed across the glomerular basement membrane to re-aggregate subepithelially accompanied by C3 deposition after 1 day. Ag-Ab complexes without C3 accumulated in the inter-podocyte space within 1 day and were seen in the epithelial cells at 6 h. C5b-9 complexes were found in subepithelial immune deposits and in membrane vesicles of the epithelial cells, but only in very small amounts in subendothelial immune deposits. Accumulated platelets, PMN, and monocyte were in direct contact with endothelial cells or subendothelial IC. PMN and monocytes contained Ag, Ab and C3 in intracytoplasmic vacuoles. Ag-Ab complexes were also found in the mesangial matrix adjacent to the subendothelial region after 2 h and increased slightly in number, with expansion of the mesangial area thereafter. Most ICs formed in the subendothelial space rapidly formed lattices of a size that activated C3 and were then translocated to the subepithelial space. The potential ability of C3 to solubilize ICs in the subendothelial region may be important in this process. Endocytosis of subendothelial ICs by PMN and/or monocytes and the movement of ICs to the mesangial matrix may also contribute to the removal of IC from the subendothelial space.
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PMID:Glomerular handling of immune complex in the acute phase of active in situ immune complex glomerulonephritis employing cationized ferritin in rats. Ultrastructural localization of immune complex, complements and inflammatory cells. 924 33

In this study, we examined the roles of C4 and C3 in immune complex glomerulonephritis by actively immunizing C4-deficient (C4 -/-), C3 deficient (C3 -/-) and wild-type mice with apoferritin. Wild-type animals with an intact complement system produced anti-apoferritin IgG and IgM antibodies, and developed mesangial proliferative glomerulonephritis characterized by hypercellularity, matrix expansion, deposition of IgG, IgM, IgA and C3, and the presence of electron dense deposits. In the majority of animals, the peripheral capillaries also contained IgG, C3 and subendothelial and subepithelial electron dense deposits. In contrast to wild-type animals, all apoferritin-immunized C4 -/- and C3 -/- mice had serum cryoprecipitates containing polyclonal IgM and the variable presence of polyclonal IgG. These animals also developed immune complex glomerulonephritis, but their disease manifestations were distinctly different from that of their wild-type littermates. In apoferritin-immunized C4 -/- and C3 -/- mice, IgG was either absent or present in reduced quantities in glomeruli, yet IgM and IgA were present in greater intensity in glomeruli. Capillary wall IgG deposits were absent in all C4 -/- and C3 -/- animals. C4 -/- animals also had significant glomerular C3 deposition, hypercellularity and neutrophil infiltration, which were not present in C3 -/- animals. These results illustrate the complex interplay between the effects of complement to process immune complexes and to lead to inflammation and tissue injury.
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PMID:Immune complex glomerulonephritis in C4- and C3-deficient mice. 946 Oct 92

Balkan nephropathy (BEN) is commonly associated with urothelial cancer. Urothelial cancer is manifested in the advanced stage of disease. The aim of this study was to facilitate early detection of urothelial cancer in BEN patients and their family members living in an endemic region by using tumour markers, carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA), and a putative marker, ferritin. Fifteen BEN patients with normal renal function, 17 with renal failure (BEN-RF), 13 healthy members of their families (HFM), 14 patients with glomerulonephritis (GN) and 12 healthy controls (C) were studied. Serum CEA levels in BEN patients were within normal limits, however, in BEN-RF patients they were significantly increased over HFM (p<0.05). Serum TPA levels in BEN and BEN-RF patients were significantly higher than in the C and HFM groups (p<0.05). Urinary CEA was not significantly different between the groups studied. Urinary TPA levels in HFM (median 125 U/l, BEN (236 U/l) and BEN-RF (275 U/l) were significantly increased over C (30 U/l), however, TPA levels were increased also in GN patients (437 U/l). None of the BEN patients studied developed urothelial cancer during the ten years' follow-up. Markedly elevated urinary TPA-like levels in all patients studied (HFM, BEN, BEN-RF, GN) suggest that urinary TPA may not be a reliable tumour marker. However, the clinical relevance of high TPA levels in BEN patients should be evaluated.
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PMID:Elevated tumour markers in patients with Balkan endemic nephropathy. 993 9


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