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)

A murine model of pulmonary B16 melanoma was used to study the infiltration into metastases of lymphokine-activated killer (LAK) cells and adherent lymphokine-activated killer (A-LAK) cells and, specifically, to study whether A-LAK cells are able to leave the tumor microcirculation and establish cell-to-cell contact with malignant cells. Fluorescence microscopy demonstrated that A-LAK cells accumulated in metastases twice as efficiently as LAK cells during interleukin-2 stimulation. Electron microscopy of pulmonary metastases 16 hours after administration of 2.5 x 10(7) A-LAK cells revealed A-LAK cells, identified by the presence of typical two-compartment granules, in direct contact with melanoma cells. This finding was confirmed by using A-LAK cells prelabeled with polycationized ferritin. In conclusion, our observations demonstrate unambiguously the ability of adoptively transferred A-LAK cells to establish contact with extravascular metastatic melanoma cells.
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PMID:Establishment of cell-to-cell contact by adoptively transferred adherent lymphokine-activated killer cells with metastatic murine melanoma cells. 206 37

The object of this study was to determine the known laboratory parameters, tumor markers and immunomodulatory substances in 69 ascites of various etiology, and to test their diagnostic significance. The usual parameters such as protein content, LDH ratio, albumin quotient and albumin gradient, fibronectin, cholesterol and cell count did not reliably differentiate the etiology in each particular case, although the mean values of the various groups differed significantly. Even cytological investigation was negative in 6 out of 29 malignant ascites. Neither were the immunomodulatory substances such as neopterin, beta 2-microglobulin and interleukin-2 receptors suitable for differentiation. In patients with carcinoma of the prostate the values of prostate-specific antigen were significantly increased in ascites. The best separation between benign hepatic or cardiac ascites and malignant ascites was provided by ferritin (sensitivity 97%, specificity 100%). The values in benign hepatic or cardiac ascites were lower than 150 ng/ml and those in malignant ascites higher than 170 ng/ml.
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PMID:[Tumor markers and immunomodulator substances in ascites--their value as screening and diagnosis parameters]. 247 98

Peripheral blood mononuclear cells (PBM) pulsed with lectin (PHA or Con A for 0.25-3 hr) show a low expression of interleukin-2 and transferrin receptors (IL-2Rs, TfRs) and a mild decline of intracellular ferritin level, compared to control cultures grown in continuous presence of mitogen. Interestingly, lectin-pulsed PBM do not release detectable amounts of IL-2 in the medium. Furthermore, expression of TfRs in these lymphocytes is not inhibited by addition of excess anti-IL-2 neutralizing monoclonal antibody, but is significantly inhibited by treatment with iron salts. These observations suggest that mitogen triggers an IL-2-independent expression of TfRs, at least in part via a decrease of intracellular iron level. Addition of either recombinant IL-2 (rIL-2) or an iron chelator (picolinic acid) to lectin-pulsed PBM induces both a marked enhancement of TfR synthesis and a sharp decline of intracellular ferritin level, which are comparable to the corresponding pattern observed in control cultures. Conversely, addition of iron salts fully inhibits the increase of TfR expression induced by rIL-2. These observations strongly suggest that the enhanced TfR synthesis elicited by rIL-2 is mediated by depletion of a regulatory intracellular iron pool. In line with these studies, greater than 99% purified T lymphocytes stimulated by lectin show a low expression of TfRs, which is markedly enhanced by addition of exogenous rIL-2. Altogether, we postulate that: (i) in resting T lymphocytes the gene encoding TfR is apparently in a 'closed' configuration; (ii) even in the absence of IL-2 activity, a mitogen pulse is sufficient to initiate the expression of TfRs, at least in part via a decline of intracellular iron level; and (iii) TfR synthesis is then largely amplified by IL-2, again via a decrease of the size of a regulatory intracellular iron pool.
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PMID:Mechanisms underlying T-lymphocyte activation: mitogen initiates and IL-2 amplifies the expression of transferrin receptors via intracellular iron level. 313 96

1. Measurements of T-lymphocyte surface ferritin using flow cytometry show that phytohaemagglutinin (PHA) stimulation causes a marked increase in the number of cells bearing spleen-type (S) and heart-type (H) ferritin on their membrane, whereas no such change occurs in non-stimulated cells. This coincides with increases in interleukin-2 receptors, transferrin receptors and HLA-DR antigen. 2. There is an increase in the intracellular concentration of both S- and H-ferritin in lymphocytes after PHA stimulation: H-ferritin increases five- to seven-fold, but S-ferritin only two-to three-fold. The maximum H/S ratio is about 15/1. However, these increases also occur in cells cultured in the absence of PHA. 3. Small amounts of both S- and H-ferritin are released into the medium, especially from stimulated cells, but the H/S ratios are lower than intracellular ratios. 4. The present findings suggest that lymphocyte stimulation followed by ferritin synthesis is accompanied by an increase in the amount of intracellular and cell surface ferritin and, possibly, the amount released from the cells.
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PMID:The response of intracellular and surface ferritin after T-cell stimulation in vitro. 350 Aug 21

The effects of iron deficiency on immunity remain controversial. This study was designed to assess the impact of iron supplementation on the immune status, in 81 children aged 6 months-3 years, at high risk for iron deficiency, using a longitudinal double blind randomised and placebo-controlled study. Lymphocytes of iron-deficient children produced less interleukin-2 in vitro. Iron supplementation for 2 months increased mean corpuscular volume, serum ferritin and serum transferrin, but had no effect on the parameters of T-cell mediated immunity. The lower interleukin-2 levels in iron-deficient suggest that cell-mediated immunity may be impaired in iron deficiency.
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PMID:The immune response in iron-deficient young children: effect of iron supplementation on cell-mediated immunity. 844 18

Interleukin-2 (IL-2) controls the proliferation of the murine T cell line B6.1 and induces transferrin receptor (TfR) mRNA steady-state levels 50-fold when added to arrested, IL-2-deprived cells. In addition, TfR mRNA is post-transcriptionally regulated by intracellular iron. Low iron levels activate a cytoplasmic RNA-binding protein, called iron regulatory factor (IRF) or iron-responsive element-binding protein, which coordinately stabilizes TfR mRNA and inhibits ferritin mRNA translation. Since ferritin expression is known to be modulated by cytokines, we decided to investigate the mechanism by which IL-2 activates TfR gene expression in B6.1 cells. Induction by IL-2 of both nuclear and cytoplasmic TfR RNA was compared with run-on transcription rates in isolated nuclei. The results revealed a 3-fold increase in TfR gene transcription and a 6-fold rise in nuclear TfR RNA reaching its steady-state level within 2 h. The main accumulation of mature mRNA in the cytoplasm occurred after 6 h in parallel with the activation of IRF. However, stimulation of IRF binding activity by the iron chelator desferrioxamine, in the absence of IL-2, failed to induce TfR mRNA. Moreover, deprivation of growing B6.1 cells of IL-2 resulted in cell arrest and a rapid decay of TfR mRNA, which was not prevented by the activation of IRF with desferrioxamine. TfR mRNA stabilization appears, therefore, to depend on IL-2. We conclude that TfR mRNA expression is controlled by at least three steps at the onset of cell proliferation: (i) the growth factor-dependent activation of transcription; (ii) mRNA stabilization by IRF in the cytoplasm; and (iii) an additional IL-2-dependent activity which prevents TfR mRNA degradation. Our results indicate that expression of TfR, like ferritin, is controlled by both iron and cytokines.
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PMID:Interleukin-2-dependent transcriptional and post-transcriptional regulation of transferrin receptor mRNA. 851 48

Placental isoferritin (PLF), an acidic isoform of ferritin, and its unique superheavy chain of 43 kDa (p43) has been described to be synthesized by human breast cancer cells. Physiologically, p43 PLF produced by the placenta is involved in immune suppression of maternal lymphocytes aimed at fetal antigens. A study was carried out to elucidate a paradigm of p43 occurrence in breast cancer patients. Immunosuppression of cytotoxic CD8+ lymphocytes was measured via inhibition of blast transformation in concanavalin A (ConA) stimulated peripheral blood lymphocytes (PBL) using 3H-thymidine uptake in vitro. PBLs were cultivated from 29 women having benign lesions in the breast as well as from 41 patients with breast adenocarcinoma. In breast cancer patients addition of p43 significantly inhibited the activation of lymphocytes proliferation by ConA compared to women with benign tumors. The addition of indomethacin or levamisole did not influence this inhibitory effect of p43 in breast cancer patients. Presence of interleukin-2 in cultures was able to overcome the inhibitory effect of p43 on CD8+ lymphocytes proliferation from women having breast adenocarcinomas and to increase its value in patients with benign lesions.
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PMID:Immunosuppressive activity of lymphocyte mitogenesis by breast cancer-associated p43. 899 59

Twenty-two different protein measurements were taken in the serum and ascitic fluid of fifty consecutive patients in an attempt to investigate which tests are the most reliable for the differential diagnosis of ascites. Serum and ascitic fluid total proteins (TPR), albumin (ALB), lactate (LAC), ferritin (FER), C3 and C4 complement factors, C-reactive protein (CRP), ceruloplasmin (CER), alpha2-macroglobulin (alpha2MG), haptoglobin (HAP), alpha1-antitrypsin (alpha1AT), alpha1-acid glycoprotein (alpha1AG), transferrin (TRF), immunoglobulins IgG, IgA, IgM and cytokines such as interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were measured to distinguish between malignant and cirrhotic ascites. Correlations and non-parametric Mann-Whitney tests were used for ascitic fluid:serum ratio comparisons between the two groups. Multivariate analyses were used to determine the most significant biochemical ratio predictors for the differential diagnosis and a recursive partitioning model was constructed. Highly positive correlations (r>0.50) were found between the ratios IgA, IgG, IgM, CER, alpha2 MG, HAP, alpha1AT, alpha1AG and TRF. There was evidence that TPR, ALB, LAC, FER, IgG, CER, alpha2MG, alpha1AT, alpha1AG, TRF and IL-8 ascitic fluid:serum ratios are significnatly higher in patients with malignant neoplasms than in cirrhotics. In the recursive partitioning model the most significant parameters were found to be the ratios of albumin and IL-1alpha. The model fitted allowed for 100% correct classification of ascites. In conclusion, we have shown that a simple and very accurate model based on two ascitic fluid: serum measurements is able to differentiate between malignant and non-malignant ascites.
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PMID:Use of a variety of biological parameters in distinguishing cirrhotic from malignant ascites. 1128 54

Blockade of B7/CD28 costimulation allows human haploidentical bone marrow transplantation without graft-versus-host disease. This study shows that blockade of B7/CD28 in anergizing mixed lymphocyte reaction (MLR) cultures of peripheral blood mononuclear cells results in the generation of alternatively activated macrophages (AAMphi). In contrast, priming MLR cultures result in generation of classically activated macrophages (CAMphi). AAMphi had enhanced expression of CD14, major histocompatibility complex class II, and CD23; produced alternative macrophage activation-associated CC-chemokine 1 (AMAC-1) chemokine; and displayed increased phagocytotic activity but decreased ability for antigen presentation. Suppression subtractive hybridization revealed that although AAMphi had undergone terminal maturation and differentiation, they entered a distinct gene expression program as compared with CAMphi and selectively expressed beta2-microglobulin, lysozyme, ferritin heavy and light chain, and the scavenger receptors macrophage mannose receptor and sortilin. Anergic T cells isolated from cultures that led to the development of AAMphi produced low amounts of interleukin-2 (IL-2), IL-4, and interferon-gamma, but high amounts of IL-10. Addition of anti-IL-10 neutralizing monoclonal antibody in anergizing cultures reversed the functional characteristics of AAMphi, indicating that at least one mechanism involved in the generation of AAMphi was mediated by IL-10. Importantly, when added in MLR cultures, AAMphi suppressed T-cell responses. Therefore, besides direct inhibition of T-cell costimulation, blockade of B7/CD28 may facilitate induction of T-cell unresponsiveness by generating AAMphi. Because in healthy individuals, AAMphi are found in the placenta and lung, where they protect from unwanted immune reactivity, the results suggest that AAMphi may play a critical role in the induction of transplantation tolerance.
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PMID:Blockade of B7/CD28 in mixed lymphocyte reaction cultures results in the generation of alternatively activated macrophages, which suppress T-cell responses. 1183 May 1

Contrary to the results of direct expression, various human proteins (ferritin light-chain, epithermal growth factor, interleukin-2, prepro-ghrelin, deletion mutants of glutamate decarboxylase and arginine deiminase, and mini-proinsulin) were all soluble in Escherichia coli cytoplasm when expressed with the N-terminus fusion of ferritin heavy-chain (FTN-H). Through systematic investigations, we have found that a specific peptide motif within FTN-H has a high affinity to HSP70 chaperone DnaK, and that the peptide motif was composed of a hydrophobic core of three residues (Ile, Phe and Leu) and two flanking regions enriched with polar residues (Gly, Gln and Arg). It was also observed that all the recombinant proteins expressed with the fusion of FTN-H formed spherical nanoparticles with diameters of 10-15 nm, as confirmed by the transmission electron microscopy image. The protein nanoparticles are non-covalently cross-linked supra-molecules formed by the self-assembly function of FTN-H. Upon the formation of the supra-molecule, its size is likely to be limited by the assembly properties of FTN-H, thereby keeping the self-assembled particles soluble. This study reports on the dual function of FTN-H for fusion expression and solubility enhancement of heterologous proteins: (i) high-affinity interaction with DnaK and (ii) formation of self-assembled supra-molecules with limited and constant sizes, thereby avoiding the undesirable formation of insoluble macro-aggregates of heterologous proteins.
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PMID:Heterologous gene expression using self-assembled supra-molecules with high affinity for HSP70 chaperone. 1600 21


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