MPO is an enzyme that generates and secretes the highly potent antimicrobial agent hypochlorous acid (HOCl) during a host immune response to infection. Its production is required for the formation of neutrophil extracellular traps (NETs), a major part of neutrophil granules, which are highly effective in killing microbes and parasites. NETs are also thought to act as a barrier to prevent further pathogen penetration or to trigger host cell cytotoxicity by the release of other molecules such as reactive oxygen species. Despite these important roles, the specific mechanisms of MPO action in the formation of NETs remain unclear.

In addition to its well-known role in the oxidative destruction of bacterial cell walls, MPO is essential for activation and mobilization of neutrophils at the site of injury or infection. MPO is also the most abundant granule protein in human neutrophils, contributing up to 5% of the dry weight of the cells. It is known to be able to generate the highly effective antimicrobial reagent HOCl by oxidizing chloride and halide ions in the presence of hydrogen peroxide (H2O2). It has also been shown that a partial deficiency of MPO does not significantly affect the ability of neutrophils to make NETs.

Molecular approaches to measuring MPO activity have been developed, including assays based on the measurement of NET release of HOCl, or by using fluorescent probes for the detection of resorufin generated by the MPO-H2O2 system. However, the general mechanism by which MPO produces HOCl remains unclear. This is largely due to the fact that the enzyme does not have the requisite sulfonium-binding residues found in other mammalian peroxidases.

A recent fluorogenic assay for MPO activity uses the reaction of resorufin with H2O2. This generates a colored product that can be monitored for its absorbance at 350 nm. Fig. 1 shows stopped-flow progress curves of resorufin generation at a series of ADHP concentrations for the MPO-H2O2 system. The results are shown as the mean SEM for a total of 12 samples.

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Last-modified: 2023-10-12 (木) 20:43:03 (210d)