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

Murine erythroleukaemic cells were studied to determine whether different isoferritins have different functions. The cells were labelled with radioactive iron and the pattern of isoferritins was analysed by chromatofocussing. No change was found after iron-loading the cells but after inducing erythroid differentiation with dimethyl sulphoxide (DMSO), iron was incorporated into both more basic and more acidic isoferritins. This was compared to ferritin subunit synthesis; DMSO induced the synthesis of a third, minor subunit whereas iron-loading had no effect. The fate of murine erythroleukaemic cell ferritin iron was followed after incubations in iron-deficient medium containing DMSO; some, but not all, of the ferritin iron was mobilized and used for haem synthesis, and the remaining iron was found amongst the more basic isoferritins. Finally, sequential radioactive iron labels were used to demonstrate that the movement of iron from ferritin to haem was compatible with the 'last-in-first-out' principle, but this could not be related to different isoferritins. These results show firstly that DMSO changes the pattern of isoferritins and ferritin subunits in murine erythroleukaemic cells. Secondly, iron associated with more basic isoferritins seems to be less easily mobilized for haem synthesis. These results support the concept that different isoferritins have different functions.
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PMID:Characterization of ferritin in murine erythroleukaemia cells. 345 43

Mouse (MEL) and human (K-562) erythroleukemia cell lines can be induced to undergo erythroid differentiation, including hemoglobin (Hb) synthesis, by extra cellular hemin. In order to study the effect of extracellular hemin on intracellular ferritin and Hb content, we have used Mossabauer spectroscopy to measure the amount of 57Fe incorporated into ferritin or Hb and a fluorescent enzyme-linked immunosorbent assay (ELISA) to measure the ferritin protein content. When K-562 cells were cultured in the presence of a 57Fe source either as transferrin or citrate, in the absence of a differentiation inducer, all the intracellular 57Fe was detected in ferritin. When the cells were cultured in the presence of 57Fe-hemin, 57Fe was found in both ferritin and Hb. 57Fe in ferritin increased rapidly, and after 2 days it reached a plateau at 5 X 10(-14) g/cell. 57Fe in Hb increased linearly with time and reached the same value after 12 days. Addition of other iron sources such as iron-saturated transferrin, iron citrate, or iron ammonium citrate caused a much lower increase in ferritin protein content as compared to hemin. When K-562 cells were induced by 57Fe-hemin in the presence of 56Fe-transferrin, 57Fe was found to be incorporated in equal amounts into both ferritin and Hb. However, when the cells were induced by 56Fe-hemin in the presence of 57Fe-transferrin, 57Fe was incorporated only into ferritin, but not into Hb, which contained 56Fe iron. These results indicate that in K-562 cells, when hemin is present in the culture medium it is preferentially incorporated into Hb, regardless of the availability of other extra- or intracellular iron sources such as transferrin or ferritin. In MEL cells induced to differentiate by dimethylsulfoxide (DMSO) a different pattern of iron incorporation was observed; 57Fe from both transferrin and hemin was found to incorporate in ferritin as well as in Hb.
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PMID:Effect of extracellular hemin on hemoglobin and ferritin content of erythroleukemia cells. 347 Feb 97

Purified recombinant human heavy subunit (rHF, acidic) and recombinant human light subunit (rLF, basic) ferritins were assessed for their effects in vitro on colony formation by normal human granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells. The purity of the samples was confirmed by electrophoresis in both nondenaturing and denaturing conditions and silver staining. Concentrations of 10(-8) to 10(-10) mol/L rHF caused an approximately 40% significant decrease in colony formation. Some significant activity was detected at 10(-11) mol/L, and activity was lost at 10(-12) mol/L. In contrast, rLF had no significant activity at 10(-8) to 10(-16) mol/L. rHF was significantly active against mouse bone marrow CFU-GM to concentrations as low as 10(-8) to 10(-9) mol/L. The inhibitory activity of rHF was inactivated with three different monoclonal antibodies recognizing the heavy subunit of ferritin, but not with two monoclonal antibodies recognizing the light subunit of ferritin. The inhibitory activity of rHF was similar in the absence or presence of serum, monocytes, and T lymphocytes. We and others have shown an association of a glycosylated natural acidic isoferritin (AIF) with inhibitory activity, but since the rHF was expressed in Escherichia coli and did not bind to concanavalin A, glycosylation of AIF is not an absolute prerequisite for this activity. These results demonstrate that rHF has suppressive activity in vitro and substantiate our original observations using purified natural acidic isoferritins.
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PMID:The influence of purified recombinant human heavy-subunit and light-subunit ferritins on colony formation in vitro by granulocyte-macrophage and erythroid progenitor cells. 349 Aug 84

Ultrastructural studies were performed on bone marrow aspirates from three patients with visceral leishmaniasis. The patients were moderately anaemic but showed a suboptimal increase in the absolute reticulocyte count. Serum and red cell folate concentrations and serum vitamin B12 concentrations were normal in all three cases, and serum ferritin concentrations were normal or increased. The bone marrows were hypercellular and showed erythroid hyperplasia; a high proportion of the erythroblasts showed dyserythropoietic changes. Amastigote forms of Leishmania donovani were found within bone marrow macrophages and within occasional neutrophil and eosinophil granulocytes. Electron microscopy showed the presence of many abnormal cells, which probably represented immature erythroblasts with giant lysosomes. These cells were often large, usually contained immature nuclei with relatively little condensed chromatin, had 1-20 electron dense cytoplasmic granules with an average diameter of 0.5 micron, and regularly displayed substantial rhopheocytotic activity. A few abnormal cells and intermediate and late erythroblasts appeared to have been phagocytosed by macrophages. The data indicate that dyserythropoiesis and ineffective erythropoiesis have a role in the pathogenesis of the anaemia of at least some cases of kala-azar.
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PMID:Ultrastructure of bone marrow in patients with visceral leishmaniasis. 355 59

A four-fold (P less than 0.001) mean increase in iron levels was found in 18 patients (a total of 36 courses of therapy) with ovarian cancer at the end of a 5-day course of cisplatin (40 mg/m2 per day every 4-5 weeks). The kinetics of these modifications began very early (24-48 h after initiation of therapy): they reached their maximum on the 4th-5th day, coinciding with the last drug administration, and basal levels were recovered after the 10th day. A subsequent eight-fold average increase (P less than 0.001) in ferritin serum levels, beginning 2 days after the iron changes, was observed, but showed a slower regression (after the 15th day). Reticulocyte counts were lowered (P less than 0.001) with the same time-course of the iron increases, but returned to pretreatment levels within 2 weeks. Total bilirubin and serum glutamate-pyruvate transaminase showed significantly delayed increases compared with iron. The results are in keeping with a reduced iron utilization by the erythroid precursors, but other mechanisms cannot be excluded. There is no statistical correlation between the early iron increases and the subsequent hemoglobin nadir values.
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PMID:Changes in serum iron levels following very high-dose cisplatin. 358 20

Basic red cell ferritin (RCF) content reflects the rate of iron uptake by marrow erythroid cells in patients with anaemia due to chronic inflammation which are sometimes also associated with metabolic disorders of the erythrocytes. For 29 patients with active inflammatic states of chronic rheumatoid arthritis (RA) and microcytic (mean corpuscular volume up to 80fl) or normocytic (MCV 80-95fl) anaemia respectively, the mean RCF content, irrespective of plasma ferritin levels, was determined using a recently established ELISA test. Red cell intermediates (ATP, GSH, 2.3 DP.G) were measured using conventional methods. The results revealed decreased RCF levels (2.8 +/- 1.5 ag/RBC) in 12 patients with RA and normal values (8.8 +/- 4.7 ag/RBC) in 17 patients which obviously did not correlate with the degree of the anaemia. The extent and pattern of the intermediates of RBC did not significantly vary from normal values. Thus, ATP, GSH and 2.3 DPT levels of RBC were only slightly increased up to 10%, especially in those patients with higher anaemic degrees. The findings of our study suggest that conventional indices for iron metabolic disorder in anaemic patients with chronic inflammatic disease should include peripheral microcytosis, transferrin saturation, and RCF content but could neglect plasma ferritin concentrations. Concerning the RBC metabolism this study did not disclose any further influences on iron metabolism parameters due to changes of mean cell age in patients with RA. Specific alterations which might hence produce additional functional disturbances of the erythrocytes in the peripheral microcirculation thus leading further to tissue cell damages in RA could be excluded as well.
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PMID:Red cell metabolism and ferritin levels in iron deficiency anaemia. 359 1

In order to develop a diagnostic approach to the common problem of anemia associated with alcoholism, 121 chronic alcoholics admitted to a general medical service with a low hematocrit were evaluated. Multiple contributing causes of anemia were present in most patients. Megaloblastic marrow change was found in 33.9% of patients, sideroblastic change in 23.1%, absent iron stores in 13.2%, aggregated macrophage iron in 81.0%, and acute blood loss in 24.8%. The MCV was of little value in predicting the presence of megaloblastic change unless markedly elevated (greater than 110 fl). In 15 of 41 patients with megaloblastic marrow morphology (36.6%) the MCV was normal or low. Among 40 patients with MCV values between 100 and 110 fl, megaloblastic change was not present in the bone marrow smears of 24 (60.0%). Neutrophil hypersegmentation was 95% specific but only 78% sensitive for megaloblastic change; in contrast, the presence of macroovalocytosis was 90% sensitive but only 68% specific. Serum lactic dehydrogenase, plasma folate, and erythrocyte folate levels had such low sensitivities and specificities for megaloblastic change as to be of little predictive value. Hematologic responses to folic acid were often inadequate in patients with megaloblastic morphologic changes, apparently because of associated acute and chronic illness. Our findings are consistent with the hypothesis that 2 mechanisms account for the development of megaloblastic hematopoiesis in alcoholics: induction of folate deficiency and a direct toxic effect of alcohol on erythroid precursors independent of folate depletion, as reflected by the presence of normal plasma and erythrocyte folate levels in several patients with megaloblastic change. In no patient was sideroblastic change the sole apparent cause of anemia. Megaloblastic hematopoiesis and aggregated macrophage iron frequently accompanied sideroblastic change. Examination of the blood smear revealed siderocytes in one-third of patients with sideroblastic marrows and dimorphic erythrocyte morphology in the majority. Dimorphic blood smears, however, were neither sensitive nor specific for sideroblastic change. Serum iron concentrations were usually not elevated in the group with sideroblastic abnormalities. In predicting marrow iron stores, serum iron and iron-binding capacity concentrations were often non-diagnostic or misleading. Serum ferritin levels less than 100 ng/ml, however, showed 100% sensitivity and 95% specificity for absent marrow iron stores despite the frequent presence of abnormal liver function. On the basis of our findings, practical guidelines have been formulated for the evaluation and therapy of anemia in alcohol
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PMID:Anemia in alcoholics. 374 28

The interrelationships between various components of the non-immune inflammatory response (white cell count, plasma lactoferrin, C-reactive protein, ferritin, iron and iron-binding capacity), were studied serially in a variety of inflammatory conditions including acute lobar pneumonia, active pulmonary tuberculosis, rheumatoid arthritis on gold therapy and sepsis in the face of marrow hypoplasia induced by chemotherapy. Lactoferrin concentrations paralleled the white count in all groups. They were highest in pneumonia and tuberculosis, mildly elevated in rheumatoid arthritis and markedly decreased in neutropenic sepsis. Very high initial lactoferrin concentrations were associated with a poor prognosis in acute pneumonia. C-reactive protein and ferritin concentrations remained elevated through the period of study in acute pneumonia and neutropenic sepsis, while they gradually normalised over weeks in subjects with tuberculosis or rheumatoid arthritis on therapy. In pneumonia and tuberculosis moderate hypoferraemia and a reduced iron-binding capacity were evident. In contrast, a raised percentage saturation was present in neutropenic sepsis, probably related to erythroid marrow suppression. Comparisons between ferritin, lactoferrin and C-reactive protein in the various groups supported the concept that ferritin behaves in part as an acute phase reactant and that hypoferraemia in inflammation is due to deviation of iron into ferritin stores. The suggestion that lactoferrin is responsible for the hypoferraemia and hyperferritinaemia was not supported by the present data. Iron deficiency appeared to limit the hyperferritinaemic response in rheumatoid arthritis, while erythropoietic inhibition by chemotherapy dampened the hypoferraemic response in neutropenic sepsis.
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PMID:The non-immune inflammatory response: serial changes in plasma iron, iron-binding capacity, lactoferrin, ferritin and C-reactive protein. 378 68

Serum erythropoietic activity was determined in 32 patients with beta thalassemia major and intermedia. Quantitation was performed by an in vitro bioassay using rabbit erythroid precursor cells (CFU-E) either by colony assay or by 3H-thymidine uptake. 20 polytransfused beta-thalassemic major patients had erythropoietic activity (mean 89.3 +/- 36 milliunits/ml) which was not significantly different (p greater than 0.2) from normal individuals (51.3 +/- 32 milliunits/ml). 12 untransfused patients with beta thalassemia intermedia were found to have comparable serum erythropoietic activity (p greater than 0.01). These levels were much lower than those found in patients with aplastic anemia who had a comparable degree of anemia. We have shown that the low EPO activity in thalassemic patients was not due to experimental conditions (excess of ferritin, low transferrin) nor to specific inhibitors appearing in this disease. No correlation was found between the erythropoietic activity and sex or other clinical parameters of the patients such as severity of the anemia, splenectomy, iron chelation or transfusion therapy. 4 young thalassemic children (1-2 yr of age) studied had high erythropoietic activity ranging from 661 to 5793 milliunits/ml--significantly different from normal children of the same age. It is suggested, therefore, that a decrease in serum erythropoietin levels develops during the course of the disease.
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PMID:Erythropoietin activity in the serum of beta thalassemic patients. 378 74

The bone marrow of a patient with acute undifferentiated leukemia developed unique colonies after a 14-day culture in erythropoietin (EPO)-containing methylcellulose. The colonies consisted of 20 to 200 nonhemoglobinized large blast cells. Cytogenetic analysis of single colonies revealed hypotetraploid karyotypes with several marker chromosomes that were identical to those found in directly sampled bone marrow. The concurrently formed erythroid bursts showed only normal karyotypes. No leukemic colony formation was observed in other culture systems with either colony-stimulating activity (CSA) or phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). The leukemic colonies exhibited a complete EPO-dose dependency similar to that of the patient's normal BFU-E. Although cytochemical and immunologic marker studies of the bone marrow cells failed to clarify the cell lineage of the leukemic cells with extraordinarily large cell size, ultrastructural study revealed erythroid differentiation such as siderosome formation in the cytoplasm and ferritin particles in the rhophecytosis invaginations. These findings indicate that the patient had poorly differentiated erythroid leukemia and that some of the clonogenic cells might respond to EPO in vitro. Corresponding to this biological feature, the leukemic cells were markedly decreased in number in response to repeated RBC transfusions, and partial remission was obtained. These observations suggest that erythroid leukemia distinct from erythroleukemia (M6) with a myeloblastic component, can develop as a minor entity of human acute leukemia.
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PMID:Leukemic blast cell colony formation in semisolid culture with erythropoietin: a case report of acute poorly differentiated erythroid leukemia. 380 69


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