Disease relevance of EPX

• Our data indicate that purified EPO shows significant inhibitory activity towards Mycobacterium tuberculosis H37Rv [1].
• Human eosinophil peroxidase (EPO) was purified from eosinophil granules derived from the peripheral blood of patients with eosinophilia [2].
• RESULTS: In acute bacterial infections ECP, but not EPO, was significantly raised in serum (P < 0.0001) compared with non-infected healthy subjects [3].
• RESULTS: Allergen challenges performed before rhinovirus inoculation increased the nasal output of EPO [4].
• BACKGROUND: Bronchial asthma is associated with elevated serum levels of eosinophil products, such as eosinophil protein X (EPX), but the occurrence in urine of this substance in patients with asthma has not previously been studied [5].

High impact information on EPX

• Several basic proteins have been isolated from eosinophil granules, including the major basic protein, eosinophil cationic protein, eosinophil protein-X and eosinophil peroxidase [6].
• We also studied the effect of TGF-beta on eosinophil function and found that TGF-beta inhibited the release of eosinophil peroxidase [7].
• LB+ at high concentration is viricidal to HIV-1, and, at levels where LB+ is ineffective alone, the addition of peroxidase (myeloperoxidase, eosinophil peroxidase) and a halide (chloride, iodide, bromide, thiocyanate) restore viricidal activity [8].
• H2O2 and purified human EPO, especially when bound to cell surfaces, mediated extraordinarily potent, completely Br(-)-dependent cytolysis of endothelial cells that was reversed by peroxidase inhibitors, HOBr scavengers, and competitive substrates [9].
• Bromide-dependent toxicity of eosinophil peroxidase for endothelium and isolated working rat hearts: a model for eosinophilic endocarditis [9].

Chemical compound and disease context of EPX

• The importance of EPX and LTC4/D4 in the characterization of chronic symptomatic rhinitis was also observed [10].
• CONCLUSIONS: Increased levels of EPX, MPO and tryptase were observed in stools from collagenous colitis patients, whereas the levels in IBS patients did not differ from healthy controls [11].
• RESULTS: Median ECP and EPX concentrations in serum (31.4 and 74.8 microg/L vs 15.8 and 24.3 microg/L, respectively), NALF (9.9 and 44. 9 microg/L vs 0 and 2.5 microg/L, respectively) and urine (49.4 vs 16.5 microg/mmol creatinine) were significantly raised in children with bronchial asthma compared with healthy control subjects [12].
• In this study, to clarify whether eosinophil protein X (EPX) is a marker which is distinct from leukotriene E4 (LTE4), or 11-dehydrothromboxane B2 (11DTXB2), we measured the urinary excretion of EPX, LTE4, and 11DTXB2 in 14 asthmatics who were admitted to the hospital with either an acute asthmatic attack or status asthmaticus [13].
• BACKGROUND: Epirubicin (EPX) has been found to be active in hormone-refractory prostate cancer (HRPC) patients [14].

Biological context of EPX

• Here we show that the human EPX gene maps to chromosome 17q23.1, which localizes 34 kb from the LPO and MPO genes [15].
• Because EPO expression is normal in MPO-deficient subjects, eosinophil contamination can significantly contribute to peroxidase activity in leukocytes from family members of an MPO-deficient subject and thereby undermine correct interpretation of the inheritance pattern [16].
• The amino acid sequence of human LPO has 51% similarity with those of both human MPO and EPO, suggesting that these peroxidase genes have evolved from a common ancestral gene [17].
• The eosinophil peroxidase gene forms a cluster with the genes for myeloperoxidase and lactoperoxidase on human chromosome 17 [15].
• Molecular cloning of the human eosinophil peroxidase. Evidence for the existence of a peroxidase multigene family [2].

Anatomical context of EPX

• The proportion of eosinophils in peripheral blood, and urinary eosinophil protein X (EPX), decreased in both weeks [18].
• Binding of eosinophil peroxidase to mast cell granules with retention of peroxidatic activity [19].
• Eosinophil peroxidase (EPO) also contributes to the peroxidase activity of blood leukocytes [16].
• In contrast, EPO-treated bacteria frequently had cell wall lesions and eventually underwent lysis, either in the presence or in the absence of H(2)O(2) [1].
• These studies suggest that the antigenic epitope recognized by P-ANCA-reactive serum is not determined by the homologous 68% peroxidase sequence shared by neutrophil MPO and EPO [20].

Associations of EPX with chemical compounds

• The MCG/EPO complex retained the capacity of the isolated EPO to catalyze the iodination reaction when supplemented with iodide, H2O2, and a protein acceptor and to kill microorganisms when supplemented with H2O2 and a halide (iodide, chloride) [19].
• Indeed, the MCG/EPO complex had significantly greater iodinating and bactericidal activity than the free enzyme when standardized to equal guaiacol units of peroxidase activity [19].
• MPO and EPO Compound II is relatively stable and decays gradually within minutes to ground state upon H2O2 exhaustion [21].
• They also suggest that in biological mixtures where amine groups are abundant, the trapping of EPO-generated HOBr/OBr- as N-bromoamines will serve to effectively "funnel" reactive brominating equivalents to stable ring-brominated forms of tyrosine [22].
• 3-Bromotyrosine and 3,5-dibromotyrosine are major products of protein oxidation by eosinophil peroxidase: potential markers for eosinophil-dependent tissue injury in vivo [22].

Physical interactions of EPX

• Introduction of purified eosinophil peroxidase (EPO) into the phagosome by binding the enzyme to the surface of the zymosan particles changed the hypermetabolic characteristics of superoxide production in MPO-deficient cells to more closely resemble normal cells, but had no effect on superoxide generation by the normal monocytes [23].
• Furthermore, both peroxidases bind strongly to collagen fibers, whereas only EPO binds to elastin [24].

Regulatory relationships of EPX

• These results suggest that butyrate induces MPO rather than EPO in EoL-1 cells and that the formation of nitrotyrosine in butyrate-induced cells is dependent on MPO [25].
• Inhibitors of chymotrypsin-like proteases inhibit eosinophil peroxidase release from activated human eosinophils [26].

Other interactions of EPX

• Using NO-selective electrodes and direct spectroscopic and rapid kinetic methods, we examined the interactions of NO with EPO and LPO compounds I and II and ferric forms and compared the results to those reported for myeloperoxidase [27].
• Cells not stained by monoclonal anti-EPO and anti-HNL antibodies included lymphocytes, monocytes, macrophages, squamous epithelial cells, and ciliated epithelial cells [28].
• Mutation of Met(243) into Thr, Gln, and Val, which are the corresponding residues of eosinophil peroxidase, lactoperoxidase, and thyroid peroxidase, respectively, and into Cys was performed [29].
• Theophylline did not alter lung functions but reduced ECP and EPX/EDN after prolonged treatment [30].
• After incubation with EPO, the macrophages produced large amounts of TNF and displayed an enhanced phorbol 12-myristate 13-acetate-triggered hydrogen peroxide release [31].

Analytical, diagnostic and therapeutic context of EPX

• Exposure of the amino acid L-tyrosine to EPO, H2O2, and physiological concentrations of halides (100 mM Cl-, </=100 microM Br-) produced two new major products with distinct retention times on reverse phase HPLC [22].
• EPO was extracted from the granule fraction using 0.2 mol/L sodium acetate pH 4.0, and the extract was subjected to gel chromatography on Sephadex G-75 and ion exchange chromatography on Biorex 70 [32].
• The biosynthesis of EPO was studied in marrow cells from patients with eosinophilia using labeling with (14C)-leucine, followed by immunoprecipitation with anti-EPO, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fluorography for visualization of labeled EPO [32].
• CONCLUSIONS: EPO, a unique component of eosinophils, and HNL, a unique component of neutrophils, are useful markers for the identification of eosinophils and neutrophils, respectively, in sputum and bronchoalveolar lavage fluid [28].
• The released amounts of MPO, ECP, and EPO in the perfusion fluids were determined by radioimmunoassays before and during prednisolone enema treatment and related to clinical, endoscopical, and histopathological data in addition to treatment outcome [33].

References