Myeloperoxidase (MPO) is an enzyme member of the subfamily of peroxidases. It is most abundantly expressed in immune cells, such as neutrophilic polymorphonuclear leukocytes (neutrophils) and lymphocytes, monocytes, and macrophages, and is also produced in other body cells. Myeloperoxidase is stored in cytoplasmic membrane-bound azurophilic granules, and during stimulation, these granules are secreted out to the extracellular space by degranulation or exocytosis. The complete biochemical mechanism of neutrophil degranulation is unclear, but oxidative stress is crucial in releasing MPO from these cells.
Neutrophils are well-known white blood cells (WBCs) playing a pivotal role in innate immunity and frontline defense against microbial attacks. In addition to MPO, several other proteins or enzymes are present in neutrophils which also show antimicrobial properties, e.g., defensins, serine proteases, cathepsin G, alkaline phosphatase, lysozyme, NADPH oxidase, collagenase, lactoferrin, cathepsin, and gelatinase, etc. Among these antimicrobial agents, MPO is the most abundant, constituting 5% dry weight of neutrophils and 25% of the azurophilic granular proteins.
Normally, neutrophils degranulate at the infection site to combat different microbial activities and help cure diseases. However, any unusual expression and release of MPO from activated neutrophils intensifies the inflammation and tissue damage and may result in several other diseases, even in the absence of infection.
Activated neutrophils, monocytes, and some tissue macrophages release MPO at the sites of inflammation, using H2O2 to oxidize several substrates, such as halides (Cl−, Br−, and pseudohalides like thiocyanate (SCN−). This reaction leads to the formation of various oxidizing radicals, such as hypochlorous acid (HOCl−), hypobromic acid (HOBr−), and hypothiocyanic acid (HOSCN). These species are potent oxidants, which are toxic to several microorganisms under normal and controlled circumstances and play an essential role in the immune system. However, excessive or unregulated production of these oxidants can damage host cells and result in several diseases.
In addition to the antipathogenic or bactericidal role of MPO-derived HOCl- during normal conditions, under some pathological circumstances, the overproduction of these oxidizing agents also causes oxidative damage to proteins and DNA in host cells. Several types of tissue injuries and the pathogenesis of various chronic diseases, such as atherosclerosis, cancer, renal disease, lung injury, and multiple sclerosis. Additionally, Alzheimer’s and Parkinson’s diseases have been reported to be directly/indirectly linked with MPO-derived oxidants. Thus, the enhanced level of MPO is one of the best inflammatory and oxidative stress markers among these commonly occurring diseases.
