Less toxic treatment options for patients with myeloperoxidase (MPO)-ANCA-associated GN are needed. Using an established murine model of focal necrotizing GN mediated by autoimmunity to MPO (autoimmune anti-MPO GN), we assessed the capacity for nasal tolerance induced by nasal insufflation of the immunodominant nephritogenic MPO peptide (MPO409-428) to attenuate this disease. Compared with mice...

Production of nitrogen dioxide by the activity of myeloperoxidase (MPO) in the presence of nitrite is now considered a key step in the pathophysiology of low-density lipoprotein (LDL) oxidation. This study shows that betanin, a phytochemical of the betalain class, inhibits the production of lipid hydroperoxides in human LDL submitted to a MPO/nitrite-induced oxidation. Kinetic measurements incl...

The functional properties of granulocytes in a diabetic patient deficient in myeloperoxidase (MPO) were compared with those of granulocytes in healthy subjects. The granulocytes of this patient had normal phagocytic activity. The microbicidal activity of the granulocytes was partially diminished with regard to Staphylococcus aureus and was almost nil with regard to Candida albicans. Fungicidal ...

The antimycobacterial role of eosinophil peroxidase (EPO), one of the most abundant granule proteins in human eosinophils, was investigated. Our data indicate that purified EPO shows significant inhibitory activity towards Mycobacterium tuberculosis H37Rv. On a molar basis, this activity was similar to that exhibited by neutrophil myeloperoxidase (MPO) and was both dose and time dependent. In c...

Myeloperoxidase (MPO) synthesis is known to be associated with the promyelocyte stage of myeloid differentiation. In particular the downregulation of MPO gene transcription is associated with myeloid cell maturation. We examined the changes in the deoxyribonuclease I hypersensitive sites within the 5' end of the MPO gene and its 5' flanking region during dimethyl sulfoxide (DMSO)-induced differ...

We intratracheally administered lipopolysaccharide (LPS) to ICR mice and then collected BAL fluid and lung tissue to determine whether levels of neutrophils and/or myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) fluid reflect lung tissue damage. Robust neutrophil accumulation into the alveolar space and lung tissue were almost completely abolished at seven days along with oxidative stress...

Activation of neutrophils induces generation of reactive oxygen species and release of granule enzymes, which not only participate in the bactericidal mechanisms of these cells, but also in possible tissue damage. We studied the effect of carvedilol (CARV) [0.1-100 micromol/l], an antihypertensive and cardiovascular drug with antioxidative properties, on superoxide generation (SO) and myelopero...

Myeloperoxidase (MPO) is a prime candidate for promoting oxidative stress during inflammation. This abundant enzyme of neutrophils uses hydrogen peroxide to oxidize chloride to highly reactive and toxic chlorine bleach. We have identified 2-thioxanthines as potent mechanism-based inactivators of MPO. Mass spectrometry and x-ray crystal structures revealed that these inhibitors become covalently...

A study was undertaken to evaluate the ability of flow cytometric analysis of intracellular myeloperoxidase (MPO) in differentiating populations of lymphocytes (L), monocytes (M) and granulocytes (G), by means of lysed whole blood method. Anticoagulated blood from 23 normal individuals was lysed with FACS lysing solution and permeabilized with FACS permeabilizing solution before subjected to di...

The SIEFED ("Specific Immunological Extraction Followed by Enzymatic Detection") method already developed for the specific detection of the activity of equine myeloperoxidase (MPO) was adapted for the specific measurement of active human MPO in biological fluids or tissue extracts. The method consists of the extraction of MPO from aqueous solutions by immobilized anti-MPO antibodies followed by...