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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thymus-derived (T) cells obtained from three categories of in vitro antigen-induced proliferative responses were assayed as sources of helper T cells. These categories are exemplified by (a) direct stimulation of keyhole limpet hemocyanin (KLH)-primed cell with KLH, which results in high indexes of proliferation; (b) direct stimulation of apoferritin-primed cells with apoferritin, which does not result in indexes of proliferation above background levels; (c) trans-stimulation of unprimed cells with X-irradiated KLH-primed cells which results in indexes of proliferation comparable to category (a). Our results indicate that levels of [3H]thymidine incorporation by proliferating populations are not an accurate reflection of helper T cell generation. Directly stimulated KLH and apoferritin-primed cells give rise to highly enriched populations of antigen-specific helper T cells which support both IgM and IgG antibody responses in vitro. Moreover, these specific helper T cells are functionally restricted by products encoded by the I region of the major histocompatibility complex (MHC). Helper T cells generated in KLH-trans-stimulated cultures are not KLH-specific in that comparable levels of helper activity are expressed using either KLH or apoferritin as carriers. These non-KLH-specific helper T cells only support the production of IgM antibody in vitro and they are not functionally restricted by MHC products.
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PMID:Helper activity of T cells stimulated in long-term culture. 9 11

This investigation demonstrates that low concentrations (25 microM) of free and transferrin-bound iron reduce the efficiency of the interferon-gamma (IFN-gamma) signal in the human myelomonocytic cell line THP-1, as seen by decreased production of neopterin, reduced degradation of tryptophan, and impaired expression of major histocompatibility complex (MHC) class II antigens. This inhibitory effect of iron, which is not due to an enhanced cytotoxicity towards THP-1 cells, is increased by enhancement of iron concentrations in a dose-dependent relationship and can be partially reversed by increasing amounts of the cytokine. The iron-mediated inhibition of the effects of IFN-gamma is fully reversed when iron is administered concomitantly with equimolar concentrations of the iron chelator deferoxamine. Furthermore, deferoxamine alone is even able to enhance the efficiency of the IFN-gamma signal. Our data provide evidence that there is an inverse correlation between the intracellular amount of iron, which is not bound to ferritin, and the activity of the IFN-gamma signal. This suggests that iron withholding by the immune cells in the course of inflammatory disorders may also contribute to the enhancement of the cytopathic effect of IFN-gamma. This speculation is confirmed by the observation of high concentrations of immune activation markers such as IFN-gamma and neopterin and low serum iron levels in patients with hypoferric anemia in the course of chronic inflammation.
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PMID:Iron modulates interferon-gamma effects in the human myelomonocytic cell line THP-1. 158 6

A previous study conducted on a group of Afrikaans-speaking subjects in the south-western Cape indicated a high frequency (0.115) of the HLA-linked iron-loading gene which causes idiopathic haemochromatosis. The results of phenotypic and genotypic studies on the first degree relatives of identified homozygotes and heterozygotes are now reported. There was considerable heterogeneity of phenotypic expression in the group of heterozygotes, with overlap between the homozygous and heterozygous subjects. The heterozygous relatives of heterozygous index cases, who had been identified on the basis of a serum ferritin concentration greater than 400 micrograms/l, appeared to have more frequent and more marked abnormalities of iron measurements than the heterozygote relatives of homozygous index cases (serum ferritin value greater than 400 micrograms/l, percentage transferrin saturation greater than 60). This suggests that the screening test was identifying a group of more significantly affected heterozygotes, with biochemical abnormalities that overlapped with the identified homozygotes. The index cases were followed up over a period of 5 years and during this time the 7 subjects diagnosed as heterozygotes showed a progressive increase in serum ferritin concentrations, which suggests some iron accumulation. Individual pedigrees included instances of gene recombination within the major histocompatibility complex, and of probable false-positive genotype assignment. The overall results confirm a high frequency of the gene in this particular community.
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PMID:Phenotypic expression of the HLA-linked iron-loading gene in the Afrikaner population of the western Cape. 334 78

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

Genetic variation in the ability to recruit and activate peritoneal macrophages was examined in seven partially developed 15I5-B congenic White Leghorn chicken lines. While the ability to generate peritoneal exudate cells (PECs) was similar in all lines, major differences were observed in the numbers, composition, and functional activity of harvestable peritoneal adherent cell populations. In response to a general stimulant, Sephadex, lines .7-2 and .6-2 produced the greatest numbers of adherent peritoneal cells while lines .C-12 and .15I-5 were among the poorest responders. Macrophage percentage of adherent PECs varied between lines. 15I5 chickens produced a consistently high percentage of adherent macrophages while .6-2 birds exhibited the lowest macrophage percentage at all ages examined. Phagocytosis was used as one measure of the level of macrophage activation and similar results were obtained using both opsonized and unopsonized sheep erythrocytes; adherent peritoneal cells from lines .6-2, .7-2, and .P-13 exhibited the highest activity and .C-12, .15I-5, and background 15I5(B15) lines produced cells with the lowest phagocytic activity. In a second functional assay, the killing of Salmonella typhimurium, macrophage-rich cells from line .P-13 exhibited the lowest activity which was significantly lower than that obtained with cells from lines .6-2 and .15I-5. Antigen-specific stimulation of peritoneal adherent cells by ferritin also showed that .C-12 was a low responder in contrast with other lines. The results indicate that these genetic lines differ in peritoneal macrophage function and suggest that the chicken major histocompatibility complex may influence certain properties of chicken macrophage function.
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PMID:Genetic variation in the recruitment and activation of chicken peritoneal macrophages. 351 94

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

We report the successful coreconstitution of solubilized lymphocyte plasma membranes and Sendai virus envelopes into membrane vesicles that possess the ability to fuse efficiently with mouse splenocytes of thymocytes to give fully viable cells with modified surface properties. Integration of donor membrane components into the acceptor cells was demonstrated by chemical, morphological, and immunological methods. Over 40% of the label from vesicles coreconstituted with radiolabeled (with 125I or 3H) lymphocyte membranes was incorporated into the fused cells. Insertion of biotin-labeled membrane components into the membranes of the acceptor cells was shown by electron microscopy with ferritin-conjugated avidin. Transfer of receptors to soybean agglutinin was also demonstrated. When vesicles from thymocyte membranes were fused with B splenocytes, over 50% of the cells were lysed with anti-theta antiserum and complement. Moreover, lymphocytes into which allogeneic membranes were incorporated triggered the autologous cells in the mixed lymphocyte reaction, indicating the functional transfer of major histocompatibility complex antigens. These findings strongly suggest that the transferred membranes were functionally incorporated into the acceptor cell membranes. The technique described opens new ways for elucidation of the role of the lymphocyte membrane in the immune response as well as for the understanding of the structure-function relationship of membrane components in other cells.
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PMID:Alteration of lymphocyte surface properties by insertion of foreign functional components of plasma membrane. 626 Dec 48

Genetic hemochromatosis (GH) is closely associated with genes of the major histocompatibility complex (MHC) on chromosome 6. Recently, a candidate gene for GH, with structural similarities to MHC class I genes, designated HLA-H and presently named HFE, has been cloned. The HFE gene is localized telomeric to the MHC and several reports have indicated that the HFE gene is mutated in GH patients. In the present study we have analyzed the relationship of HFE gene variants and disease manifestation in GH patients and family members. Fifty-seven patients with GH, 73 family members and 153 healthy blood donors were studied for the amino acid dimorphism at codon 63 (His63Asp=H63D) and codon 282 (Cys282Tyr= C282Y) of the HFE gene. The codon 63 and 282 dimorphism were defined by PCR amplification of genomic DNA samples and restriction enzyme digestion using RsaI/SnaBI for C282Y and BclI/MboI for H63D. Ferritin, transferrin serum levels and total iron-binding capacity were determined prior to therapeutic intervention. The Tyr-282 substitution occurred in 53 (93%) of patients compared with 8 (5.2%) of controls (OR=169, P<0.0001). Fifty-one (90%) patients were Tyr-282 homozygous. In contrast, the Asp-63 substitution was present in 5 (8.8%) of the patients compared with 34 (22%) of controls (OR=0.39, P=NS) with none of the patients being homozygous. In Tyr-282 homozygous GH patients serum ferritin levels, transferrin saturation, liver iron and liver iron index were elevated significantly compared to Tyr-282-negative patients, whereas no difference was observed between Tyr/Cys-282 heterozygous and Tyr-282-negative patients.
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PMID:HFE codon 63/282 (H63D/C282Y) dimorphism in German patients with genetic hemochromatosis. 955 Mar 27

Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder of iron metabolism. More than 80% of HH patients are homozygous for a point mutation in a major histocompatibility complex (MHC) class I type protein (HFE), which results in a lack of HFE expression on the cell surface. A previously identified interaction of HFE and the transferrin receptor suggests a possible regulatory role of HFE in cellular iron absorption. Using an HeLa cell line stably transfected with HFE under the control of a tetracycline-sensitive promoter, we investigated the effect of HFE expression on cellular iron uptake. We demonstrate that the overproduction of HFE results in decreased iron uptake from diferric transferrin. Moreover, HFE expression activates the key regulators of intracellular iron homeostasis, the iron-regulatory proteins (IRPs), implying that HFE can affect the intracellular "labile iron pool." The increase in IRP activity is accompanied by the downregulation of the iron-storage protein, ferritin, and an upregulation of transferrin receptor levels. These findings are discussed in the context of the pathophysiology of HH and a possible role of iron-responsive element (IRE)-containing mRNAs.
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PMID:HFE downregulates iron uptake from transferrin and induces iron-regulatory protein activity in stably transfected cells. 1057 8

Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism, resulting in an increased iron deposition and multiorgan failure. Recently a candidate gene of HH, termed HFE, has been identified on chromosome 6, coding for a protein homologous to major histocompatibility complex (MHC) class I molecules. Two mutations of the hemochromatosis gene leading to an exchange of cysteine to tyrosine at aminoacid 282 and histidine to asparagine at aminoacid 63, are retained responsible for the development of hereditary hemochromatosis. The Cys282Tyr-mutation disrupts a disulfid bond and thus abrogates binding of the mutant HFE-protein to beta 2-microglobulin and its presentation on the cell surface. The His63Asp-mutation seems to play a role in pH-regulated dissociation of the transferrin receptor/transferrin complex in the lysosome. Mutations of the HFE-protein alter the affinity of the transferrin receptor for its ligand transferrin and may thus cause an intracellular accumulation of iron. Knowledge of the responsible gene allows a molecular diagnosis of HH. The new genetic marker can be used for screening and confirmation of HH reducing the need for confirmatory liver biopsies. Compared to standard screening parameters like ferritin and transferrin saturation genetic testing will allow the diagnosis of HH in an early, asymptomatic state before iron accumulation has occurred. As a normal life expectancy of patients with HH can be achieved if iron reduction is initiated early, genetic testing may thus be of great benefit for patients with HH.
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PMID:[Hereditary hemochromatosis--new developments after discovery of the HFE gene]. 1066 43


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