Disease relevance of Mpo

• In the current studies we used genetically altered mice deficient in MPO to investigate the role of the enzyme in host defense against the Gram-negative bacterium Klebsiella pneumoniae, an important human pathogen [1].
• When challenged i.p., mice deficient in either MPO or NE were markedly more susceptible to bacterial infection and death [1].
• MATERIALS AND METHODS: Body weight, histological scores, and myeloperoxidase activity were evaluated in trinitrobenzene sulfonic acid colitis [2].
• The effects of NK1-R genetic deletion/antagonism on pancreatic plasma extravasation, amylase, myeloperoxidase (MPO), and histology in cerulein-induced pancreatitis were characterized [3].
• H(2)S alone could also cause lung inflammation, as evidenced by a significant increase in lung myeloperoxidase activity and histological evidence of lung injury [4].

High impact information on Mpo

• This pathology was independent of bacterial overgrowth and was characterized by increased myeloperoxidase activity, moderate degeneration of myenteric neurons, and intraluminal hemorrhage [5].
• The capacity of drugs to serve as myeloperoxidase substrates in vitro was associated with the ability to induce lupus in vivo [6].
• Using single cell RT-PCR we show that erythroid (beta-globin) and myeloid (myeloperoxidase) gene expression programs can be initiated by the same cell prior to exclusive commitment to the erythroid or granulocytic lineages [7].
• Myeloperoxidase (MPO), which accumulates in the infarct zone, is released from neutrophils and monocytes leading to the formation of reactive chlorinating species capable of oxidizing proteins and altering biological function [8].
• MPO(-/-) demonstrated decreased leukocyte infiltration, significant reduction in LV dilation, and marked preservation of LV function [8].

Chemical compound and disease context of Mpo

• At the end of the experiment, following decapitation, lung, liver and kidney tissue samples were taken for histological examination or determination of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO) activity and collagen contents [9].
• Antibiotic treatment perturbed gut flora, increased MPO and SP immunoreactivity in the colon, and produced visceral hypersensitivity [10].
• Capsazepine treatment significantly reduced the level of NK1R endocytosis, and this was associated with similar reductions in pancreatic MPO activity and histological severity of pancreatitis [11].
• Mice treated with CP-96345, either prophylactically, or therapeutically, were protected against acute pancreatitis and associated lung injury as evident by attenuation in plasma amylase, pancreatic and pulmonary myeloperoxidase activities, and histological evidence of pancreatic and pulmonary injuries [12].
• After leukocyte degranulation, MPO localized in and around vascular endothelial cells in a rodent model of acute endotoxemia and impaired endothelium-dependent relaxant responses, to which MPO-deficient mice were resistant [13].

Biological context of Mpo

• Two of the latter genes, Mpo and Ngfr, mapped to mouse chromosome 11 [14].
• There is significant homology between the murine and human MPO genes in the 1.6-kb region located upstream of the murine MPO transcription initiation sites [15].
• B6 mice were treated with spantide, and after infection, slit lamp examination; clinical score; bacterial counts; and myeloperoxidase (MPO), RT-PCR, ELISA, and polymorphonuclear (PMN) cell chemotaxis assays were performed [16].
• Tissue samples of the liver were taken for histological examination or for the determination of levels of malondialdehyde, an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase activity, an index of tissue neutrophil infiltration [17].
• Conclusion: These studies reveal that early dermal inflammatory responses including MPO activity, production of MIP-2, KC, and IL-1beta are impaired in mice given ethanol before injury, which may also have detrimental affects on later stages of wound healing [18].

Anatomical context of Mpo

• This response is associated with diminished mucosal activity of the neutrophil enzyme myeloperoxidase compared with that of wildtype mice [19].
• The myeloperoxidase (MPO) gene is expressed specifically in myeloid cells [15].
• 5',3', and internal deletions of this DNA segment localized several cis-acting DNA elements in the murine MPO promoter which are functional in 32D cl3 cells, a murine myeloblast cell line which expresses MPO [15].
• The mucosa of colon tissues showed reduction of myeloperoxidase activity and attenuated staining for intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 [20].
• RESULTS: Organ damage was significantly reduced by hIL-10 gene transfer, which was associated at the tissue level with reduced MPO activity in the liver, lung, and kidney and decreased leukocyte sequestration and MDA formation in the lung [21].

Associations of Mpo with chemical compounds

• In addition to being an air pollutant, NO2 is a potent inflammatory oxidant generated endogenously by myeloperoxidase and eosinophil peroxidase [22].
• Acetaminophen caused a significant decrease in the GSH level of the tissue, which was accompanied with significant increases in the hepatic luminol and lucigenin chemiluminescence values, malondialdehyde level, MPO activity and collagen content [17].
• Results: At 12 and 24 hours after injury, MPO in wounds from ethanol-exposed mice was significantly reduced compared with wounds from vehicle-treated animals [18].
• Only the benzodiazepine antagonist inhibited the lung myeloperoxidase activity [23].
• Anti-inflammatory activity of GJE glycoprotein was assessed by neutrophil infiltration and colonic lipid peroxidation, and determined by myeloperoxidase (MPO) activity and levels of thiobarbituric acid reactive substances (TBARS), respectively in DSS treatment system [24].

Physical interactions of Mpo

• Significant increases in SP, increased myeloperoxidase levels coupled with local morphological deterioration of the jejunum and impaired lymphocyte responses to exogenous SP in vitro have been associated with the model [25].
• Similarly, TNF-alpha binding protein (175 mg/kg) attenuated LPS-induced myeloperoxidase activity (6.04 +/- 0.14 U/g lung wet wt; P < 0.05) [26].
• Inhibition of the alpha-ketoglutarate dehydrogenase complex by the myeloperoxidase products, hypochlorous acid and mono-N-chloramine [27].

Enzymatic interactions of Mpo

• Application of TPA to mouse skin induces oxidative stress, as evidenced by numerous biochemical responses, including significant generation of H2O2 and enhanced levels of myeloperoxidase and oxidized glutathione reductase activities and decreases in glutathione levels and superoxide dismutase activity [28].

Regulatory relationships of Mpo

• To test the pathogenic potential of antibodies alone, purified anti-MPO IgG or control IgG was injected intravenously into Rag2(-/-) mice and wild-type mice [29].
• The RANTES antagonist Met-RANTES significantly (P < 0.01) reduced the toxin A-induced increases in ileal fluid accumulation and myeloperoxidase activity in wild-type mice [30].
• However, expression of the Evi-1 gene blocked the ability of the cells to express myeloperoxidase and to terminally differentiate to granulocytes in response to G-CSF [31].
• Consistent with that interpretation, the addition of purified MPO enzyme to cultured macrophages inhibited iNOS induction by IL [32].
• Neutrophil infiltration increased gradually 24 hours after ICAM-1 and VCAM-1 were upregulated with significant elevation of myeloperoxidase activity over baseline at 72 hours (7.2 +/- 1.2 vs. 18.1 +/- 2.2 activity units/gram tissue; P <0.05) [33].

Other interactions of Mpo

• The murine myeloperoxidase promoter contains several functional elements, one of which binds a cell type-restricted transcription factor, myeloid nuclear factor 1 (MyNF1) [15].
• Diminished pulmonary chemokine mRNA production was associated with reduced neutrophil margination and pulmonary myeloperoxidase activity [34].
• 4. Of interest, the systemic administration of an anti-TNF-alpha antibody produced a significant inhibition of paw oedema, mechanical allodynia and MPO activity [35].
• KC ( approximately 400 pg x mg protein(-1), n=12) and MIP-2 (approximately 800 pg x mg protein(-1), n=12) proteins peaked at day 7, together with myeloperoxidase (MPO) activity [36].
• An antiserum to MCP-1 reduced NAG activity at day 21 but increased MPO activity values (n=8, P<0.05) [36].

Analytical, diagnostic and therapeutic context of Mpo

• Regional assignment of the gene by in situ hybridization localized Mpo to the region C-E1, with a peak at band 11C [37].
• We studied acute myocardial infarction (AMI) in a chronic coronary artery ligation model in MPO null mice (MPO(-/-)) [8].
• Cross-sectional analysis of the aorta indicated that lesions in MPO-deficient mice were about 50% larger than controls [38].
• Here, we show that inhaled chrysotile asbestos fibers cause increased myeloperoxidase activity in bronchoalveolar lavage fluids (BALF) and myeloperoxidase immunoreactivity in epithelial cells lining distal bronchioles and alveolar ducts, sites of initial lung deposition of asbestos fibers [39].
• Genetic dissection of vasculitis, myeloperoxidase-specific antineutrophil cytoplasmic autoantibody production, and related traits in spontaneous crescentic glomerulonephritis-forming/Kinjoh mice [40].

References