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 role in the pathogenesis of immune complex-mediated glomerulonephritis of C5 or some terminal complement component dependent upon C5 for activation was explored in a congenic strain of C5 sufficient (NSN) and C5 deficient (OSN) mice. When these mice were given daily injections of heterologous protein, horse apoferritin (HAF), there were profound differences between the strains in the development of glomerulonephritis and renal dysfunction. When NSN and OSN mice produced low levels of anti-HAF, NSN mice developed extensive glomerular deposits of HAF and immune reactants and a mild proliferative glomerulonephritis. In contrast, comparable OSN mice developed only trace mesangial localization of HAF and no glomerular lesions by light microscopy. When NSN and OSN mice produced high levels of anti-HAF, both strains had equivalent glomerular immune deposits; however, NSN mice developed a severe necrotizing and crescentic glomerulonephritis, while OSN mice had much less glomerular injury. Compared to OSN mice, these NSN mice also had much more severe tubulointerstitial injury, and significantly higher serum creatinine levels. Thus, in this experimental model, the absence of C5 resulted in reduced glomerular immune complex localization when there were small amounts of circulating immune reactants; and in markedly reduced glomerular leukocyte influx, necrosis and crescent formation, when large amounts of immune reactants have localized in glomeruli. These effects could be mediated by C5 (such as C5a) or by some terminal complement component(s) dependent upon C5 for activation.
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PMID:Immune complex induced glomerular lesions in C5 sufficient and deficient mice. 294 91

Male BALB/c mice given daily intraperitoneal injections of 4 mg of horse-spleen apoferritin develop, in the majority of cases, a proliferative and necrotizing glomerulonephritis with leukocytic infiltration and extensive intraglomerular thrombosis within 10 to 14 days, as previously reported. We now show that if injection of the antigen is discontinued, surviving animals develop extensive glomerulosclerosis (GS). Ten of 13 mice treated as indicated above and sacrificed 4 months after the last horse-spleen apoferritin injection developed segmental GS involving over 40% of their glomeruli. Tubulointerstitial damage of proportionate severity also developed. Ultrastructurally, pronounced mesangial expansion due to matrix deposition obliterated the glomerular architecture. We offer this as a reproducible model of immune complex-mediated GS particularly suited to the study of cellular interactions involved in the pathogenesis of GS.
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PMID:Immune complex acute necrotizing glomerulonephritis with progression to diffuse glomerulosclerosis. A murine model. 297

The effects of increasing two dietary polyunsaturated fatty acids, eicosapentaenoic and linoleic, on the glomerulonephritis induced by repeated injections of apoferritin in the mouse were studied. Urinary protein excretion was measured serially; serum creatinine, aortic and renal production of eicosanoids and kidney histology were measured at sacrifice at 8 weeks. Both high EPA and LA feedings were associated with lesser proteinuria, normalization of renal function and profound changes in the tissue production of prostaglandin and thromboxane, which may explain their protective effect in this model of renal disease.
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PMID:Protective effect of polyunsaturated fatty acid supplementation in apoferritin induced murine glomerulonephritis. 301 61

In pharmacologic doses E series prostaglandins attenuate the development of immune complex nephritis. We studied the effect of the dietary prostaglandin precursor linoleic acid on murine apoferritin-induced immune complex glomerulonephritis. High, normal, or low linoleic acid diets were fed to mice for 4 weeks prior to and during the intraperitoneal apoferritin administration. A high linoleic acid diet feeding was associated with less proteinuria, less renal histologic damage, and prevented a rise in serum creatinine. We conclude that linoleic acid has a protective effect on the development of murine apoferritin-induced immune complex nephritis.
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PMID:Effects of dietary linoleic acid enrichment on induction of immune complex nephritis in mice. 315 80

The relationship between hypertension, ferritin-antiferritin mesangial immune injury (FIC), and progressive glomerular damage was studied in hypertensive (8% NaCl chow) Dahl salt-sensitive rats (DS) and in spontaneously hypertensive rats (SHR). The glomeruli of SHR are protected from the increased perfusion pressure that accompanies systemic hypertension by preglomerular vasoconstriction, while the glomeruli of hypertensive DS are not. Blood pressure, serum creatinine levels, urinary protein excretion, and glomerular injury (assessed by semiquantitative morphometric analysis) were determined in 20-week-old SHR and DS with FIC. In addition, half of a group of 20-week-old SHR with FIC were uninephrectomized and progression of glomerular injury was assessed 12 weeks later. Control rats for each of the groups did not receive FIC. Our studies showed that more extensive mesangial expansion and glomerulosclerosis developed in hypertensive DS with FIC than in rats without FIC. Glomerular injury in DS with FIC affected cortical and deep glomeruli. Similarly, hypertensive SHR with FIC had minimal damage in cortical glomeruli. In deep glomeruli of SHR, mesangial expansion was similar to that of DS, but glomerulosclerosis was absent. In SHR, a 50% reduction in renal mass, a maneuver known to decrease preglomerular vasoconstriction, resulted in mesangial expansion similar to that in DS in cortical glomeruli while deep glomeruli developed mesangial expansion as well as glomerulosclerosis. Our results suggest that when hypertension and mesangial immune injury coexist with renal vasodilatation (as occurs in DS with 2 kidneys and in SHR after uninephrectomy), they act synergistically to induce progressive glomerular damage. Similar mechanisms may be operative in hypertensive humans with glomerulonephritis and may condition the rate of progression to renal insufficiency.
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PMID:Role of hypertension in progressive glomerular immune injury. 315 4

The role of the major histocompatibility complex in the development of apoferritin induced immune complex glomerulonephritis was studied in H-2 congenic B10 mice. The glomerular lesions varied strikingly among the three different strains studied. The B10 (H-2b) mice had minimal mesangial expansion or no lesions at all. The B10.BR (H-2k) mice had mesangial expansion and proliferative glomerulonephritis without crescents or interstitial mononuclear cell infiltration. In contrast, the B10.D2 (H-2d) mice had necrotizing glomerulonephritis with crescents and an interstitial mononuclear cell infiltrate. Immunofluorescence and electron microscopy demonstrated only minimal mesangial deposits in B10 (H-2b) mice, predominantly mesangial deposition in the B10.BR (H-2k) mice, and mesangial and subepithelial immune complex deposits in B10.D2 (H-2d) mice. These morphologic differences correlated with functional abnormalities. Only the B10.D2 (H-2d) mice developed proteinuria, hematuria, and elevated blood urea nitrogen. They also had the most elevated antiapoferritin IgG levels. These experiments demonstrate that differences in the pathologic lesions and susceptibility to immune complex glomerulonephritis can be seen in animals that differ only at the H-2 locus. This model will lend itself to the study of the mechanisms by which the major histocompatibility complex influences the development of immune complex glomerulonephritis.
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PMID:The role of H-2 in apoferritin-induced murine immune complex glomerulonephritis. 337 15

In order to explore the pathogenic mechanism of proteinuria in glomerulonephritis, ultrastructural changes of the glomerular basement membrane were investigated in rats with chronic serum sickness induced by repeated intravenous injections of bovine serum albumin (experimental rats). Rats injected with saline served as controls. The animals were sacrificed and examined 13 weeks after treatment, when the mean urinary protein of experimental animals reached 206 mg/24h/100g body weight. Enhanced transcapillary passage of anionic ferritin was observed in experimental rats. Purified glomerular basement membranes of control and experimental rats were examined by electron microscopy after negative staining. The glomerular basement membrane of experimental rats had enlarged pores. The results suggest that an increase in the radius of glomerular pores may be responsible for proteinuria in glomerulonephritis.
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PMID:Changes in the molecular sieve of the glomerular basement membrane of rats with chronic serum sickness. 338 99

Three inbred strains of mice were identified which demonstrated different susceptibilities to induction of immune complex glomerulonephritis (ICGN) despite sharing the same major histocompatibility complex haplotype (H-2k). Groups of mice from each of these three strains, B10.BR, CBA and C3H/HeJ, were injected with one of two different dose schedules of horse apoferritin (HAF) for 4 weeks, after which glomerular morphology, immunoglobulin deposition, and serum anti-HAF antibody levels were examined. With either dose schedule, only those mice which demonstrated a high level antibody response developed ICGN and glomerular immunoglobulin deposition. These results suggest that susceptibility to ICGN in this model is related to the level of antigen exposure and to the magnitude of the antibody response, which is not under strict control of the major histocompatibility complex.
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PMID:Variable susceptibility to immune complex glomerulonephritis among mice sharing the same major histocompatibility complex. 379 59

The effects of treatment with 16,16-dimethyl prostaglandin E2 (DMPGE2) on histologic damage, glomerular immune complex deposition, serum total IgG subclass levels, anti-apoferritin IgG levels, and peripheral blood T-lymphocyte subsets were determined in apoferritin-induced immune complex glomerulonephritis of mice. The results demonstrate that doses of DMPGE2 ranging from 2.5 to 10 micrograms twice daily significantly reduced the degree of glomerular damage in a dose-dependent manner. Similarly, these doses of DMPGE2 reduced the amount of immunoglobulin deposition along peripheral capillary loops. Total IgM, IgG1, IgG2a, and IgG2b were unaffected by DMPGE2 administration. Serum anti-apoferritin IgG levels were significantly reduced in mice receiving DMPGE2 at doses of 5 and 10 micrograms twice daily. Nephrotic mice had significantly reduced peripheral blood total T lymphocytes (Lyt-1+) and a reduction of T-suppressor (Lyt-2+) cells. Administration of DMPGE2 at doses of 5 and 10 micrograms twice daily prevented these T-lymphocyte alterations. These studies indicate that treatment of mice receiving apoferritin with DMPGE2 may prevent glomerulonephritis by altering both cellular and humoral immune responses.
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PMID:Alterations in serum antibody and peripheral T-lymphocyte subsets resulting from treatment of murine immune complex glomerulonephritis with PGE2. 387 Nov 80

Monocytes infiltrate glomeruli during mesangial deposition of ferritin, and during experimental glomerulonephritis. To determine whether this is solely a local phenomenon, leucocyte infiltration in other organs has been studied following intravenous ferritin injection. Lewis rats received an i.v. injection of 150 mg ferritin/100 g body weight. At 24 h there was a peripheral blood leucocytosis (ferritin-treated rats 26.32 +/- 13.7, control rats 8.54 +/- 2.41 X 10(6) cells/ml) due to increase in polymorphs and monocytes. Bone marrow cell counts fell (ferritin-treated rats 49 +/- 7, control 80 +/- 11 X 10(6)/100 g body weight). Cell counts on cell suspensions of perfused, enzyme-digested lung, liver and spleen, and lung lavage showed major significant increases in total cell counts: lung 250 +/- 36 (89 +/- 16), lung lavage 2.6 +/- 0.8 (1.4 +/- 0.5), liver 140 +/- 37 (60 +/- 11), spleen 306 +/- 38 (200 +/- 27) X 10(6)/100 g body weight (control values in parentheses). Cytospin preparations of these suspensions, stained for non-specific esterase showed that the increase in cell numbers was due to increases in non-specific esterase-positive cells (monocytes) and polymorphs. These results demonstrate a generalized leucocyte mobilization, sequestration, and tissue infiltration after i.v. ferritin. The renal glomerulus therefore is not the only site of leucocyte accumulation. These findings may have relevance for studies on inflammation mediated by leucocytes in models of experimental immune complex glomerulonephritis.
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PMID:Blood leucocyte infiltration after intravenous injection of ferritin in the rat. 387 62


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