Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Here, we briefly review the molecular biology of the human eosinophil granule proteins, major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). The nucleotide sequence of MBP cDNA indicates that MBP is translated as a 25.2-kilodalton preproprotein; the mpb gene consists of 6 exons and 5 introns spanning 3.3 kilobases (kb). The approximately 2.1-kb nucleotide sequence of EPO cDNA corresponds to a prosequence, light chain and heavy chain in that order; similarities to other peroxidases suggest the existence of a multigene family. EDN and ECP cDNAs and genes are remarkably similar throughout, suggesting a relatively recent divergence. Promoter regions of the 4 genes show interesting differences and similarities which may be related to differential gene regulation.
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PMID:The molecular biology of eosinophil granule proteins. 165 92

Segmental antigen bronchoprovocation was used to define the nature of the inflammatory process in allergic airway disease. Bronchoalveolar lavage fluid obtained from allergic rhinitis patients 12 min after segmental antigen instillation (immediate response) revealed a significant increase in histamine and tryptase, but no cellular response. Repeat segmental lavage 48 h later (late response) showed marked and significant increases in both low and normal density eosinophils as well as striking elevations of eosinophil granular protein levels (major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and eosinophil peroxidase). Leukotriene C4, but not tryptase, concentrations were also consistently elevated in late lavage samples. Further, the late lavage samples showed a significant increase in interleukin-5 concentrations that correlated with the presence of eosinophils and eosinophil granular proteins. Neither eosinophils nor soluble mediators of eosinophils increased when normal subjects were similarly challenged with antigen. These data suggest that eosinophils are attracted to the airway during the late-phase allergic reaction and that IL-5 may produce changes in airway eosinophil density and promote the release of granular proteins to cause airway injury.
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PMID:Immediate and late airway response of allergic rhinitis patients to segmental antigen challenge. Characterization of eosinophil and mast cell mediators. 174 38

Umbilical cord mononuclear cells, HL-60 cells, HL-60 clones selected for eosinophil differentiation, and the eosinophil leukemia cell line EoL were tested for their ability to produce eosinophil peroxidase. HL-60 clones selected for eosinophil differentiation produced eosinophil peroxidase, as judged by staining of cells for cyanide-resistant peroxidase activity; however, these cells lost their ability to produce eosinophil peroxidase in long-term culture. In contrast, eosinophil precursors from human umbilical cord blood mononuclear cells stimulated with murine EL-4 conditioned medium (EL-4 CM) were regularly induced to eosinophil protein synthesis, including eosinophil peroxidase, major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin, as assessed by cyanide-resistant peroxidase and immunofluorescence staining. This induction by EL-4 CM is either at the level of gene transcription or mRNA stabilization, as shown by the increase of total mRNA for eosinophil peroxidase, major basic protein, and eosinophil-derived neurotoxin by Northern blot analyses. Purified peripheral blood eosinophils incubated for 4 days with EL-4 CM had increased survival over control eosinophils. Moreover, this enhanced survival was specifically blocked by antiserum to interleukin 5. Our results suggest that the effects of EL-4 CM on human umbilical cord mononuclear cells and mature eosinophils are due to the presence of interleukin 5.
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PMID:Eosinophil differentiation of human umbilical cord mononuclear cells and prolonged survival of mature eosinophils by murine EL-4 thymoma cell conditioned medium. 187 84

Recently four tissue toxic proteins namely major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) were found in eosinophilic leucocytes. Although the characteristics of these proteins concerning tissue damage in the local site of type I allergic reaction have been investigated mainly in lower respiratory tract, the actual clinico-pathological roles of these proteins in nasal allergy are not clarified. Contrary, eosinophils also have histaminase, arylsulfatase, phospholipase D, which are considered to act on a negative feedback mechanism in allergic reaction through inactivation of chemical mediators. Therefore, estimation of ECP and simultaneously arylsulfatase B in nasal secretion and the sera from patients with nasal allergy may clarify the dynamics of clinico-pathological state, especially in the late phase of allergic reaction in each patients. ECP concentrations in the nasal secretions from 22 patients and in the sera from 12 patients with nasal allergy were measured by RIA method. The activities of arylsulfatase B in the nasal secretions and the sera were also estimated in the same specimens as ECP by measuring its hydrolytic activity using p-nitro cathecol sulfate as a substrate. The results obtained were as follows; 1) There was a significant correlation between ECP concentrations in the nasal secretions and the severities of clinical symptoms, especially the degree of nasal obstruction. ECP concentrations also significantly correlated to the score of eosinophilic leucocytes in the nasal smears. 2) The serum ECP concentrations significantly correlated to the number of eosinophilic leucocytes in the peripheral blood, and also showed slight tendency of correlation to the severity of clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Study on eosinophil cationic protein (ECP) and arylsulfatase B in nasal secretions and sera from patients with nasal allergy]. 188 31

The secretion of preformed granule proteins by eosinophils is an important correlate of eosinophil activation. However, a review of the literature reveals large disparities in the amounts of these substances which were reportedly secreted when eosinophils were activated. In the present study we report that our attempts to quantitate the secretion of eosinophil peroxidase and eosinophil-derived neurotoxin from activated eosinophils by measuring these substances in the incubation supernatants were uniformly unsuccessful. We found that, once they were secreted, both eosinophil peroxidase and eosinophil-derived neurotoxin were promptly lost to assay and presumably destroyed. Thus the measurement of the difference in the concentration of these substances in eosinophils prior to and after activation, revealed that as much as 65% of the eosinophil-derived neurotoxin and 62% of the peroxidase in the eosinophils were lost to assay during activation of the cells whereas the largest amount of these substances which could be measured in the incubation supernatants never exceeded 2%. Evidence is presented that the destruction of eosinophil-derived neurotoxin must occur prior to the release of this substance into the medium. Attempts to inhibit the destruction of eosinophil peroxidase and of eosinophil-derived neurotoxin by incorporating various inhibitors into the incubations were unsuccessful. These results emphasize the need to monitor the overall recoveries of secreted products from activated eosinophils and suggest that meaningful estimates of the secretion of these granule proteins from activated eosinophils can only be obtained by measuring the residual content of these substances in eosinophils after they have been activated and comparing these values to the contents of eosinophils prior to activation.
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PMID:Pitfalls in the quantitative estimation of the secretion of granule proteins by eosinophils. 191 27

In this study we attempted to compare cord blood derived, in vitro differentiated eosinophils to peripheral blood eosinophils with respect to their capacity to respond to various activators and, therefore, their potential ability to contribute to an inflammatory response. The cells were compared with respect to their density, content of eosinophil peroxidase, and eosinophil-derived neurotoxin, and with respect to their responses to various activators. The in vitro cultured, cord blood derived eosinophils were distinctly lighter than the freshly isolated peripheral blood cells. This difference in cell density was reflected in a slightly reduced content of both eosinophil peroxidase (1.17 +/- 0.29 compared to 2.03 +/- 0.22 arbitrary units/2,000 cells) and eosinophil-derived neurotoxin (18.7 +/- 4.0 vs. 26.4 +/- 4.5 ng/10(4) cells). We compared the cells with respect to two different activation end points; the production of activated oxygen metabolites (superoxide anion) and the secretion of cationic proteins from their granules (eosinophil peroxidase and eosinophil-derived neurotoxin). In general, these responses were either the same in the two cell populations, or they were only slightly lower in the cord blood derived cells. There were, however, a few notable exceptions. Thus the secretory responses of the cultured cells to C5a and C3a anaphylatoxins and O2- production with the chemotactic peptide, formyl-methionyl-leucyl-phenylalanine, and with aggregated IgG were consistently greater than those of the normodense eosinophils. The possible implications of these differences on the state of maturation of the in vitro differentiated eosinophils are briefly discussed.
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PMID:How similar are in vitro differentiated, cord blood derived eosinophils to peripheral blood eosinophils? A comparison of their peroxidase and eosinophil-derived neurotoxin contents and of their responses to various activators. 196 30

Eosinophil infiltration and degranulation around the tissue-invasive stages of several species of helminths have been observed. Release of eosinophil granule contents upon the worms is supported by localization of two of the major granule proteins, major basic protein (MBP) and eosinophil peroxidase (EPO), on and around species of trematodes, nematodes, and cestodes. In the case of filarial worms, MBP is deposited on degenerating microfilariae (mf) of Onchocerca volvulus. Here, we performed in vitro assays of the toxicity of four purified eosinophil granule proteins, namely, MBP, EPO, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), for the mf of Brugia pahangi and Brugia malayi. MBP, ECP, and EDN killed these worms in a dose-related manner although relatively high concentrations of EDN were necessary. EPO, in the presence of a H2O2-generating system and a halide, was the most potent toxin on a molar basis; here, the most potent halide was I- followed by Br- and Cl-. Surprisingly, EPO in the absence of H2O2 killed mf at concentrations comparable to those required for MBP and ECP. The toxicity of EPO + H2O2 + halide was inhibited by heparin, catalase, or 1% BSA, whereas the toxicity of EPO alone was inhibited only by heparin. Heparin also inhibited killing by both MBP and ECP. Despite the homology of ECP with certain RNases, placental RNasin, an RNase inhibitor, was unable to inhibit ECP-mediated toxicity. These results indicate that all of the eosinophil granule proteins are toxic to mf and they support the hypothesis that eosinophil degranulation causes death of mf in vivo.
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PMID:In vitro killing of microfilariae of Brugia pahangi and Brugia malayi by eosinophil granule proteins. 232 97

The eosinophil granule major basic protein, the eosinophil cationic protein, and the eosinophil-derived neurotoxin were found to be lytic for Trypanosoma cruzi trypomastigotes from blood, cell cultures, or insect vectors and for cultured amastigotes. The toxic effects of the major basic and cationic proteins were inhibited by the polyanions heparin and dextran sulfate, in keeping with the cationic nature of these proteins, or by heat denaturation, suggesting that molecular conformation was also relevant. The lytic activity of the neurotoxin was not inhibited by heating at 56 degrees C for 4 hr, establishing an additional difference with the eosinophil cationic protein. Heparin had only a slight inhibitory effect on the toxicity of the neurotoxin, and dextran sulfate was inactive even at 25 mg/ml. Although both the eosinophil cationic protein and the neurotoxin possess ribonuclease activity, only the toxicity of the latter was abolished by the ribonuclease inhibitor RNasin (Promega, Madison, Wisconsin) or by a competitive substrate, yeast ribonucleic acid. Eosinophil peroxidase significantly increased the extent of trypomastigote or amastigote killing by hydrogen peroxide in the presence of iodide. This effect was abrogated by sodium azide, bovine serum albumin, or gelatin, known inhibitors of the eosinophil peroxidase + halide + hydrogen peroxide system. These results suggest that the destruction of T. cruzi trypomastigotes and amastigotes by eosinophils may result from toxic mechanisms involving several granule proteins.
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PMID:Toxic effects produced or mediated by human eosinophil granule components on Trypanosoma cruzi. 245 44

We tested the effects of four eosinophil granule cationic proteins: major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), on guinea pig tracheal epithelium in vitro. Examination by inverted microscopy revealed that MBP, both the form stabilized by alkylation of sulfhydryl groups as well as the native form of the molecule, ECP, EPO by itself, as well as EPO + H2O2 + halide, but not EDN, cause dose-related damage to the tracheal epithelium. The lowest concentrations of MBP and ECP causing damage were 10 and 100 micrograms/ml, respectively. In contrast, EDN, although biochemically similar to ECP, did not damage the tracheal epithelium in concentrations of up to 200 micrograms/ml. MBP caused exfoliation, as well as bleb formation and ciliostasis. EPO in the presence of the H2O2-producing enzyme glucose oxidase (GO), Cl-, 0.11 M, and iodide caused ciliostasis, bleb formation, and exfoliation of epithelial cells at concentrations as low as 1 U/ml (3.9 micrograms/ml). EPO + GO in the presence of Cl-, 0.11 M, alone or with Cl- and l-, 10(-4) M, or Cl- and Br-, 5 x 10(-5) M, were all toxic to epithelium. Surprisingly, EPO by itself caused partial ciliostasis, bleb formation, and exfoliation of epithelial cells in a dose-related manner at concentrations as low as 10 to 30 U/ml (39 to 121 micrograms/ml). These results confirm prior observations showing the toxicity of MBP to tracheal epithelium and indicate that ECP and EPO alone, as well as EPO + GO + halide, cause damage. Thus, several eosinophil granule proteins are able to damage respiratory epithelium.
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PMID:Toxicity of eosinophil cationic proteins for guinea pig tracheal epithelium in vitro. 292 79

An immunohistochemical study of eosinophil distribution in the inflammatory cell infiltrates of four different types of myocardial lesions associated with Chagas' disease--caused by Trypanosoma cruzi--showed larger numbers of these cells in areas presenting tissue necrosis and degeneration, most notably in patients with the most severe myocarditis from a histopathological stand-point. Using antisera specific for human eosinophil-derived neurotoxin or eosinophil peroxidase, we detected deposits of these secretion products on myofibres and in the interstitium of chagasic myocardium displaying necrosis and degeneration but rarely in other types of lesions. These deposits were not detectable in the myocardium of non-chagasic patients who had died from myocardial infarction (acute or in the scarring stage) or myocarditis secondary to bacterial endocarditis. When human eosinophil-derived neurotoxin was incubated with myoblast monolayers there was a significant cell injury, detachment and lysis. These effects were abrogated by yeast RNA, added as a competitive ribonuclease substrate, and inhibited by the ribonuclease inhibitor RNasin, suggesting that the ribonuclease activity of the eosinophil-derived neurotoxin was involved in the effect. These results suggest a link between eosinophil infiltration and necrosis in chagasic myocardial lesions and point to EDN, and perhaps other toxic eosinophil secretion products, as possible mediators of tissue damage.
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PMID:Immunohistochemical detection of deposits of eosinophil-derived neurotoxin and eosinophil peroxidase in the myocardium of patients with Chagas' disease. 304 21


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