Disease relevance of Epx

• Immunopathogenesis of experimental ulcerative colitis is mediated by eosinophil peroxidase [1].
• Using an established mouse model of human periventricular leukomalacia, we investigated whether EPO could reduce excitotoxic damage [2].
• We conclude that a single dose of EPO is sufficient to reduce excitotoxic brain injury and may therefore possess therapeutic relevance in the clinical setting [2].
• Lung eosinophilia was evaluated by measurement of eosinophil peroxidase activity and confirmed by eosinophil counts in histologic sections [3].
• To test this hypothesis, we first incubated murine J558L plasmacytoma cells with varying combinations of drug (PSH and/or copper sulfate) plus modulators (fetal calf serum, dithiothrietol, catalase, eosinophil peroxidase) and then used fluorescence microscopy to measure cell proliferation, necrosis, and apoptosis [4].

High impact information on Epx

• Biotechnology licensing: Greens oppose EPO plant [5].
• EoPs expressed eosinophil-related genes, such as the eosinophil peroxidase and the major basic protein, but did not express basophil/mast cell-related mast cell proteases [6].
• Although migration of lymphocytes into the central nervous system was unaffected, the efficacious effects of CP-105,696 correlated with up to a 97% decrease in eosinophil infiltration into the lower spinal cord as determined by light and electron microscopy and quantitated by levels of the specific enzyme marker eosinophil peroxidase [7].
• Factors stimulating eosinophil differentiation in vitro have been studied by means of a liquid bone marrow culture system in which the number of eosinophils is estimated directly by morphology or indirectly by assay for eosinophil peroxidase [8].
• Although EPO-R expression also supports EPO-dependent proliferation of CTLL-2, a mature T-cell line, those cells did not produce globin transcripts, presumably because they lack requisite cellular factors involved in erythrocyte differentiation [9].

Chemical compound and disease context of Epx

• The Friend spleen focus-forming virus envelope glycoprotein, gp55, binds to the murine erythropoietin receptor (EPO-R) and triggers growth activation in the absence of EPO [10].
• These results are important because certain human lymphomas contain extensive extracellular deposits of eosinophil peroxidase, thereby making these tumors potentially less susceptible to killing by otherwise therapeutic doses of glucose oxidase [11].
• Synthetic antioxidants: EPO (p-ethoxyphenol), PHP (p-hydroxypropiophenone), and DPPD (N,N'-diphenyl-p-phenylenediamine) dissolved in dimethylsulfoxide were administered subcutaneously to mice after subcutaneous implantation of Lewis lung carcinoma or amelanotic B16 melanoma into the tails [12].

Biological context of Epx

• EPO-mediated upregulation of EPO-R, but not EPO, mRNA was observed within 4 h of the excitotoxic insult [2].
• Eosinophil infiltration into the local tissue was determined by examination of skin histology and eosinophil peroxidase activity [13].
• The loss of EPO had no effect on the development of OVA-induced pathologies in the mouse [14].
• The murine eosinophil peroxidase gene (Epx) maps to chromosome 11 [15].
• RESULTS: Eosinophilic infiltration into the lung was induced upon antigen inhalation in parallel with the rise in bronchoalveolar lavage fluid (BALF) eosinophil peroxidase activity [16].

Anatomical context of Epx

• These findings provide direct evidence of a central role for eosinophils and EPO in GI dysfunction and potentially the immunopathogenesis of UC [1].
• Recombinant murine (rm) interleukin (IL)-5 enhances the eosinophil peroxidase content in cells cultured in vitro compared with rmIL-3 and granulocyte-macrophage colony-stimulating factor [17].
• The results indicate that F. hepatica ES antigens, like IL-5, stimulate eosinophil maturation in bone marrow with a consequent rise in EPO activity in the cells [18].
• That is, without T-cell memory responses, no eosinophil recruitment and release of EPO (which is known to induce bronchoconstriction) occurred in the airways, and no Th2 cytokine profile was detected in the BAL fluid [19].
• Adenosine challenge significantly increased the levels of eosinophil peroxidase, neutrophil myeloperoxidase and beta-hexosaminidase in BAL [20].

Associations of Epx with chemical compounds

• Furthermore, using EPO-deficient mice and an EPO inhibitor resorcinol we demonstrate that eosinophil-derived peroxidase is critical in the development of GI dysfunction in experimental UC [1].
• When administered 1 h following intracerebral injection of 10 mug ibotenic acid at day 5 of life, both a single injection of EPO (5000 IU/kg bw) and repetitive administrations of EPO reduced white and gray matter lesion size [2].
• In addition to being an air pollutant, NO2 is a potent inflammatory oxidant generated endogenously by myeloperoxidase and eosinophil peroxidase [21].
• In addition, EPO-mediated oxidative damage of proteins (e.g., bromination of tyrosine residues) recovered in bronchoalveolar lavage from OVA-treated wild-type mice was <10% of the levels observed in bronchoalveolar lavage recovered from asthma patients [14].
• The absence of phenotypic consequences in these knockout animals extended beyond pulmonary histopathologies and airway changes, as EPO-deficient animals also displayed OVA-induced airway hyperresponsiveness after provocation with methacholine [14].

Regulatory relationships of Epx

• In contrast, C/EBPepsilon, IL-5Ralpha, and eosinophil peroxidase mRNAs were induced in response to IL-3 and IL-5 after transfer onto OP9 cells [22].
• It was found that the presence in all cultures (including those from control animals) of either ES antigens at an optimal concentration of 100 micrograms ml-1 (established in preliminary trials) or IL-5 at 500 units ml-1 led to enhanced EPO activity [18].

Other interactions of Epx

• Two days after the last challenge, the allergic airway inflammation was evaluated by cellular migration, eosinophil peroxidase (EPO) activity, cytokine and chemokine production and pulmonary mechanical parameters [23].
• Then, we evaluated the effects of Y-24180, ketotifen, suplatast and prednisolone on the increase in EPO activity, IL-4 and IL-5 [24].
• With regard to the correlation between eosinophil maturation and EPO acquisition, eosinophil cells cultured with rmIL-5 expressed significantly more EPO activity than those generated in the presence of rmIL-3 and GM-CSF [17].
• To characterize interleukin (IL)-5-induced eosinophils, we examined the expression of CD44, very late antigen (VLA)-4, and the IL-5 receptor alpha chain, as well as the levels of eosinophil peroxidase and the generation of superoxide [25].
• The kinetics of blood eosinophils, eosinophil peroxidase (EPO) in bone-marrow cells, serum levels of IgE and Af-specific antibodies, Af-induced cytokine production and mRNA, and lung histology were studied [26].

Analytical, diagnostic and therapeutic context of Epx

• Intraperitoneal injection of TRFK-5 in mice exposed to A. fumigatus antigen produced a significant reduction in eosinophils (PB 6.6 +/- 1.14% vs. 3.8 +/- 0.8%, P < .01) and EPO production in BM (0.935 +/- 0.03 vs. 0.615 +/- 0.02, P < .001) [27].
• HD Ad vectors are thus excellent tools for EPO gene therapy [28].
• Total IgE, Af-specific IgG1 (enzyme-linked immunosorbent assay) in serum, and eosinophils (eosinophil peroxidase assay) in lungs and bone marrow were measured [29].
• This study uses eosinophil peroxidase (EPO) histochemistry and transmission electron microscopy (TEM) analysis to assess eosinophil degranulation in the airways of ovalbumin (OVA)-sensitized and challenged BALB/c and C57BL/6 mice [30].
• When EPO was added to this coculture, the number of induced floating cells increased twofold to threefold [31].

References