Myeloperoxidase

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Functions of Myeloperoxidase

• Reactions of hypochlorous acid. Oxidative equivalents formed by MPO are involved in numerous processes of tissue damage. Hypochlorous acid is known to oxidize at a significant rate sulfhydryl and thioether groups of proteins [34, 35]. It chlorinates amino groups to chloramines [36, 37]. Because of its strongly cationic properties, MPO is known to be easily attached to negatively charged biological membranes [38]. Thus, reactions with unsaturated bonds of different phospholipids are also quite possible. The formation of chlorohydrins as well as lysophospholipids in unsaturated phosphatidylcholines by hypochlorous acid and by the MPO-H2O2-Cl- system has been recently described [39-41]. MPO products are also involved in initiation of lipid peroxidation. Peroxidation by hypochlorous acid is favored by the presence of hydroperoxides previously accumulated in lipid material [42, 43]. The one-electron oxidation of different substrates by complex I of MPO causes radical products such as tyrosyl radical, which is also known to initiate lipid peroxidation processes [44, 45].
• Attachment of myeloperoxidase to membranes. Plasma levels of free MPO are often elevated in patients during inflammatory conditions [46, 47]. This strongly cationic protein binds to the negatively charged endothelial plasma membrane, whereby this binding depends on the presence of heparin/heparan-containing glycosaminoglycans [48, 49]. Moreover, cell-bound myeloperoxidase rapidly transcytoses the intact endothelium and localizes at the basolateral site of the endothelium closely associated with interstitial matrix proteins such as fibronectin [49].
• Protein nitration by myeloperoxidase. Nitration of free and protein-bound tyrosine correlates well with myeloperoxidase activity under inflammatory conditions [50, 51]. Compound I of MPO is able to oxidize nitrite to the nitrating species nitrogen dioxide (NO2) at a significant rate [21]. In inflammatory models, the immunoreactivity of MPO strongly co-localizes with the formation of nitrotyrosine in subendothelial and epithelial tissue regions [52].
• Modulation of the vessel tonus. Myeloperoxidase impairs NO-dependent blood vessel relaxation and guanylate cyclase activation in an inflammatory model by regulating the availability of nitric oxide [53]. This effect is favored by endothelial localization of secreted MPO [52] and the high rate of NO oxidation by radical products of MPO catalysis [22, 23, 53].
• Termination of PMN responses. Myeloperoxidase also modulates a variety of aspects of the inflammatory response. It is assumed that the MPO-H2O2-halide system inactivates some of the secreted granule contents, decreases the binding of formylated peptides to chemotactic receptors, and influences other functions in stimulated PMNs [54]. Thus, myeloperoxidase contributes to physiological feedback of recruitment of PMNs. It contributes to the termination of the influx of PMNs in inflammatory loci. MPO-deficient PMNs usually exhibit a stronger and more prolonged respiratory burst [55, 56].
• Myeloperoxidase and pathologies. Myeloperoxidase is assumed to be involved in the pathology of different diseases such as atherosclerosis, cancer, multiple sclerosis, and Alzheimer's disease [57-60]. MPO has been found in arteriosclerotic plaques