Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

We recently established a human granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell line (HML) from colony-constituent cells grown by peripheral blood cells of a patient with acute megakaryoblastic leukaemia. The HML cells possessed megakaryocytic features, as determined by cytochemical, electron microscopic and flow cytometric analysis. In the present study we examined the effects of retinoic acid (RA) on the development of HML cells. All-trans-RA, 13-cis-RA and 9-cis-RA at 10(-8) mol/l to 10(-5) mol/l inhibited the GM-CSF-dependent cell growth. Some of the RA-treated cells contained prominent azurophilic granules and were positive for peroxidase. They also reacted with Biebrich scarlet, Luxol fast blue and a monoclonal antibody against eosinophil peroxidase. In addition, exposure to RA increased the frequency and the intensity of major basic protein-positive cells. However, eosinophil-derived neurotoxin and eosinophil cationic protein were not detected or were only detected at a low level in the lysates of the HML cells treated with RA. Although IL-5 alone could not stimulate cell growth, the addition of IL-5 to the cultures containing stem cell factor + all-trans-RA was required for the expression of the eosinophilic phenotype. These results suggest that the HML cell line is a megakaryoblastic cell line with the potential to differentiate into the eosinophilic lineage. HML cells may be a useful model for elucidating the eosinophilic differentiation programme.
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PMID:Establishment of a GM-CSF-dependent megakaryoblastic cell line with the potential to differentiate into an eosinophilic lineage in response to retinoic acids. 948 39

Recent reports describe the beneficial use of lodoxamide, an anti-allergic compound, for the treatment of asthma and allergic conjunctivitis. Lodoxamide is known as a mast cell stabilizer, however, the association of a significant clinical improvement with a specific decrease in eosinophil infiltrate suggested possible direct effects of lodoxamide on eosinophils. The chemotactic response of eosinophils to fMLP as well as to IL-5, in vitro, was very significantly and dose-dependently inhibited by Lodoxamide. Lodoxamide was also able to strongly inhibit the release of eosinophil peroxidase after IgA-dependent activation and, to a lesser extent, the release of eosinophil cationic protein and eosinophil-derived neurotoxin. Moreover, the release of cytotoxic mediators evaluated in an antibody-dependent cytotoxicity assay against parasitic targets was also significantly reduced, not only in the case of human eosinophils but also in a rat eosinophil-mast cell model of cytotoxicity. Taken together, these results indicate that lodoxamide can exert potent inhibitory effects on eosinophil activation in vitro combined with a strong inhibition of eosinophil attraction, leading therefore to a reduction in their pathological potential in vivo.
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PMID:Inhibitory effects of lodoxamide on eosinophil activation. 965 7

A new human leukemia cell line with an eosinophilic phenotype, designated YJ, was established from the peripheral blood cells of a patient with chronic myelomonocytic leukemia (CMMoL) with eosinophilia. When cultured in RPMI 1640 medium containing 10% fetal bovine serum, most YJ cells were myeloblastoid with a small number of the cells having eosinophilic granules. Cell surface markers in the YJ cells were positive for CD33 and were negative for CD34, CD16 and CD23. The eosinophilic characteristics of YJ cells were confirmed by histochemical staining with Fast-Green/Neutral-Red and by the expression of mRNAs for eosinophil-associated granule proteins, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), eosinophil peroxidase (EPO), and major basic protein (MBP), and for the Charcot-Leyden crystal (CLC) protein. The YJ cells could be induced towards monocytic differentiation by stimulation with phorbol 12-myristate 13-acetate (PMA). The monocytic characteristics of YJ cells treated with PMA were confirmed by morphological analysis with alpha-naphthyl butyrate esterase staining, by CD14 expression, and by increased expression of Egr-1 mRNA. Furthermore, YJ cells could be differentiated towards the neutrophil lineage by stimulation with all-trans retinoic acid (RA). YJ cells treated in vitro with 2 microM RA differentiated into metamyelocytes and band neutrophils, and increased the number of nitroblue tetrazolium (NBT)-positive cells and increased gp91phox mRNA expression. Thus, the YJ cell line exhibited eosinophilic characteristics, but was able to differentiate to the monocytic or neutrophilic lineages in response to PMA or RA, respectively. The expression of genes for transcription factors involved in myeloid differentiation was evaluated by Northern blot analysis. Increased expression of Egr-1 was observed with macrophage differentiation. In contrast, increased expressions of C/EBPbeta and MZF-1 mRNA occurred with neutrophilic differentiation. The YJ cell line should be useful for elucidating the molecular mechanisms governing lineage switching from the eosinophil to monocytic or neutrophil lineages.
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PMID:Models of lineage switching in hematopoietic development: a new myeloid-committed eosinophil cell line (YJ) demonstrates trilineage potential. 973 93

Eosinophils, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN/EPX), myeloperoxidase (MPO) and IgE were measured in blood, serum and/or urine in Schistosoma haematobium- and Onchocerca volvulus-infected Guineans and O. volvulus- and S. haematobium-negative Guineans coinfected or infected with intestinal nematodes. The number of eosinophils and levels of eosinophil granule proteins but not of MPO were found to be strongly elevated in all Africans as compared to European controls. The highest serum ECP and serum and urinary EDN/EPX levels were observed in the hyperreactive form of onchocerciasis (sowda). Onchocerciasis patients and O. volvulus-negative Africans coinfected or infected with intestinal nematodes (hookworm and/or Ascaris lumbricoides) revealed higher serum granule protein concentrations and/or absolute eosinophil counts and urinary ECP than those without nematode infections. Statistical differences between both sections were found for the absolute eosinophil counts and for serum EDN/EPX and IgE in generalized onchocerciasis, and for urinary ECP in sowda, indicating stimulation of the eosinophil potential of O. volvulus-positive patients by coexistent hookworm infection. This worm species, in contrast to A. lumbricoides, causes especially high eosinophil counts and EDN/EPX and IgE levels. From these results it is concluded that in nematode diseases, ECP and EDN/EPX levels reflect the degree of antigenic stimulation, eosinophil activation and eosinophil turnover rates. Serum ECP and serum and urinary EDN/EPX may, therefore, serve as parameters to monitor helminth infection. Urinary ECP may be a marker of eosinophiluria secondary to urogenital manifestation of S. haematobium. It is elevated in hyperreactive onchocerciasis activated by intestinal nematodes.
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PMID:Eosinophils, eosinophil cationic protein and eosinophil-derived neurotoxin in serum and urine of patients with onchocerciasis coinfected with intestinal nematodes and in urinary schistosomiasis. 1020 16

In recent years, bronchial asthma has come to be regarded as a chronic inflammatory disease of the respiratory tract, with mast cells, lymphocytes and eosinophils playing important roles in its pathogenesis. Proteins contained in eosinophil granules, especially major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPO), can cause tissue injury. When stimulated, eosinophils release mediators such as leukotriene C4 (LTC4) and platelet activating factors (PAF). Thus, they are recognized as effector cells that are actively involved in the development of allergic inflammation. In this study, eosinophils from healthy volunteers were used to investigate the effects of Saiboku-to on eosinophils whose survival had been prolonged through stimulation with eosinophil-activating cytokines such as interleukin (IL)-3, IL-5 and granulocyte macrophage colony stimulating factors (GM-CSF). As a result, the cytokine-enhanced survival of eosinophils was significantly shortened by the addition of Saiboku-to. These findings suggest that Saiboku-to has the potential to inhibit allergic responses by directly affecting eosinophils which are related to allergic inflammation.
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PMID:Effects of saiboku-to on the survival of human eosinophils. 1042 Mar 87

We evaluated the ability of eosinophil granule major basic protein (MBP) to stimulate interleukin (IL)-8 production by neutrophils. MBP over the concentration range of 0.1 to 10 microM stimulated the release of up to approximately 8 ng/ml IL-8. Incubation with 2 microM MBP showed that, after a 1 h lag, the level of IL-8 release increased with time for approximately 10 h. At the 2 microM concentration, eosinophil cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase did not stimulate significant levels of IL-8 production. MBP stimulated 2-fold increases in IL-8 messenger RNA (mRNA) after 1 and 3 h of incubation, which were blocked by pretreatment with actinomycin D. However, stimulation with MBP did not produce an increase in the binding activity of nuclear factor (NF)-kappaB or activator protein-1. No NF-IL-6 binding activity was detected in the same nuclear extracts. In addition, stimulation with MBP prolonged the stability of IL-8 mRNA. MBP also induced transient increases in mRNA for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, but did not stimulate the release of either chemokine. These findings indicate that MBP is selective among the eosinophil granule proteins as a stimulus for neutrophil IL-8 release and, further, that stimulation of neutrophil IL-8 release by MBP involves both transcriptional and posttranscriptional regulation. We postulate that MBP-induced release of IL-8 by neutrophils may contribute to the pathophysiology of acute asthma and other inflammatory lung diseases.
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PMID:Stimulation of neutrophil interleukin-8 production by eosinophil granule major basic protein. 1042 6

Eosinophils release lipid mediators, including leukotriene C4, platelet-activating factor, and liposins, and contain four distinct granule cationic proteins, major basic protein, eosinophil peroxidase, eosinophil cationic protein, and eosinophil-derived neurotoxin, which may cause dysfunction and destruction of other cells. Eosinophils are primarily thought of as terminal effectors of allergic responses and of parasite elimination. Eosinophils are characteristically present within the airway lumina of asthmatics, and these airway eosinophils have been induced in vivo to express major histocompatibility complex II (MHC-II) complexes and costimulatory molecules, which are required for T lymphocytes to be functionally activated. In in vitro experiments, eosinophils can process antigen and express the costimulatory molecules, and after cytokine-elicited induction of MHC-II, expression can function as antigen-presenting cells in stimulating T lymphocyte responses. Airway luminal eosinophils can migrate into draining paratracheal lymph nodes, localized to T cell-rich paracortical areas, and stimulate antigen-specific T cell proliferation in vivo within paratracheal lymph nodes, which was CD80- and CD86-dependent and limited to CD4+ T cells. Furthermore, eosinophils within the lumina of airways promote expansion of T helper cell type 2 (Th2) by presenting antigen, suggesting that eosinophils actively modulate immune responses by amplifying Th2 cell responses.
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PMID:Eosinophils function as antigen-presenting cells. 1521 55

Leukotriene B4 (LTB(4)) is a potent lipid mediator of inflammation that possesses antiviral activities. Here we provide evidence that LTB(4)-mediated defense against in vitro cytomegalovirus (CMV) infection of human leukocytes involves activation of the high-affinity LTB(4) receptor (BLT1) and neutrophil degranulation. Treatment of CMV-infected peripheral blood leukocytes with LTB(4) (10 nM) leads to a significant reduction in viral titers. This activity involves neutrophil activation through the BLT1 receptor, because no reduction in viral titers was observed after neutrophil depletion from cellular preparation or when leukocytes were pretreated with the BLT1 antagonist U75,302. Direct stimulation of neutrophils with LTB(4) (in the presence or absence of CMV) leads to the release of myeloperoxidase, alpha-defensins, eosinophil-derived neurotoxin, and the human cathelicidin LL-37 in a BLT1-dependent manner. LTB(4) does not act exclusively on the secretion of preformed antimicrobial peptides, but also acts on the synthesis of selected peptides as reflected by the increase in transcriptional levels of eosinophil-derived neurotoxin (EDN) and LL-37 in LTB(4)-treated neutrophils. Treatment of cell cultures with neutralizing antibodies directed against alpha-defensins, EDN, and LL-37 significantly reduces the antiviral effect of LTB(4), suggesting that LTB(4) may act through the release of antimicrobial peptides. Ex vivo experiments using LTB(4)-treated neutrophils from peritoneal washing of wild-type and BLT1 knockout mice further supported the role played by antimicrobial peptides in LTB(4)-mediated antiviral activity toward CMV. These results provide evidence of a mechanism by which LTB(4) induces host defense against viral infection.
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PMID:Leukotriene B4-mediated release of antimicrobial peptides against cytomegalovirus is BLT1 dependent. 1793 Nov 11

Nitration of tyrosine residues has been observed during various acute and chronic inflammatory diseases. However, the mechanism of tyrosine nitration and the nature of the proteins that become tyrosine nitrated during inflammation remain unclear. Here we show that eosinophils but not other cell types including neutrophils contain nitrotyrosine-positive proteins in specific granules. Furthermore, we demonstrate that the human eosinophil toxins, eosinophil peroxidase (EPO), major basic protein, eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), and the respective murine toxins, are post-translationally modified by nitration at tyrosine residues during cell maturation. High resolution affinity-mass spectrometry identified specific single nitration sites at Tyr349 in EPO and Tyr33 in both ECP and EDN. ECP and EDN crystal structures revealed and EPO structure modeling suggested that the nitrated tyrosine residues in the toxins are surface exposed. Studies in EPO(-/-), gp91phox(-/-), and NOS(-/-) mice revealed that tyrosine nitration of these toxins is mediated by EPO in the presence of hydrogen peroxide and minute amounts of NOx. Tyrosine nitration of eosinophil granule toxins occurs during maturation of eosinophils, independent of inflammation. These results provide evidence that post-translational tyrosine nitration is unique to eosinophils.
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PMID:Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase. 1869 36

We have demonstrated that an immature prebasophilic cell line,KU812 cells can be induced to differentiate into basophil-like cells when cultured with hydrocortisone (HC) with enhanced cell surface expression of FcepsilonRI, a high affinity IgE receptor. In this study, we report that sodium nitroprusside (SNP), an intracellular NO donor, also induces cell surface expression of FcepsilonRI on KU812 cells. Cell surface FcepsilonRI expression was detected in about 20% of KU812 cells treated with SNP for 14 days as well as the cells treated with HC for 7 days, while non-treated KU812 cells did not express FcepsilonRI on their cell surface. However, Wright-Giemsa staining and flowcytometry analysis of CD13 and CD15 antigens on HC and SNP treated KU812 cells demonstrated that SNP induced eosinophilic differentiation in KU812 cells differently from HC which induced basophilic differentiation. To further confirm this result, we performed RT-PCR against mRNAs specific for eosinophils, such as eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase(EPO). SNP treated KU812 cells but not HC treated cells expressed EDN and EPO mRNA depending upon the induction of differentiation,clearly demonstrating that SNP induces eosinophilic differentiation in KU812 cells. To clarify that different signaling cascades were activated in HC and SNP treated KU812 cells, we analyzed activities of AP-1, NF-AT and NF-kappaB transcription factors by EMSA, which are known to be involved in signal transduction pathways downstream from the FcepsilonRI molecule of basophils. All these three transcription factors were activated in HC treated KU812 cells,but not in non-treated and SNP treated KU812 cells. These results indicate that KU812 cells are multi-potent precursor cells which can be induced to differentiate into basophils and eosinophils upon exogenous signals, and that NO is an important factor to decide the eosinophilic differentiation in KU812 cells with enhanced surface expression of FcepsilonRI, and further suggest that different signaling cascades can be activated between basophilic and eosinophilic differentiation in KU812 cells.
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PMID:Induction of basophilic and eosinophilic differentiation in the human leukemic cell line KU812. 1900 29


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