Review
Human myeloperoxidase in innate and acquired immunity

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Abstract

Polymorphonuclear leukocytes (PMNs) are important players in innate and acquired immunity. These cells accumulate at inflammatory sites and contribute to host defence, regulation of the inflammatory process, and also to tissue injury. One of the key components of PMNs is the heme-containing enzyme myeloperoxidase (MPO) that is stored in large amount in azurophilic granules of resting cells. Here we review the (patho)physiological role of MPO from the viewpoint of participation of PMNs in immune reactions. Myeloperoxidase is able to catalyse a wide range of one- and two-electron substrate oxidations. With special products, MPO contributes to apoptosis induction in PMNs and other cells, and, thus, to termination of inflammatory response. On the other hand, MPO released from necrotic cells promotes an inflammation by further recruitment of PMNs, and chemical modification of proteins and other tissue constituents. Myeloperoxidase is a fascinating, multifunctional, and challenging enzyme that hasn’t yet revealed all its secrets.

Section snippets

Recruitment of leukocytes

Polymorphonuclear leukocytes (PMNs,

Structural data of MPO

Myeloperoxidase (MPO) is mostly related to PMNs and to a lesser extent to monocytes. This enzyme is usually lost during monocyte maturation to macrophages. However, MPO-rich macrophage populations are found together with MPO-negative cells in human arteriosclerotic lesions [34], circulating blood [35], and multiple sclerosis lesions [36].

Eosinophil granulocytes contain a related enzyme, the eosinophil peroxidase (EPO) [37]. A further heme peroxidase involved in immune responses is the

Modulation of MPO activity

The production of HOCl and further chlorinated species is a hallmark for MPO. We next analyse different factors that may modulate the MPO-mediated oxidation of halides and other substrates under physiological relevant conditions.

Potential sites for in vivo myeloperoxidase activity

Myeloperoxidase effects are closely related to sites where PMNs accumulate. Often, the infiltration of PMNs into inflamed tissues is assessed by determination of myeloperoxidase activity. During activation of PMNs a substantial part of MPO might be released into the extracellular medium. Neutrophils undergoing necrosis also liberate MPO. This externalised MPO is able to bind to different targets and may affect these targets by their products. An overview about the main (patho)physiological

Myeloperoxidase as a potential source of damage under pathological conditions

The presence of myeloperoxidase in inflamed tissue sections is not surprising as PMNs massively accumulate at these sites. Active MPO was detected in arteriosclerotic plaques [189], [240], in brain tissue showing Alzheimer-type pathology [241], [242] or Parkinson’s disease [243], in multiple sclerosis lesions [36], in synovial fluids of patients with rheumatoid arthritis [244], [245], [246], in glomerular basement membrane in membranous glomerulonephritis [247], [248], and in PMN-mediated liver

Relation of MPO to other heme peroxidases

Compensatory mechanisms for MPO-deficiency have been assumed. An increased number of blood eosinophils have been reported in congenital MPO-deficiency [294]. To what extent, eosinophil peroxidase (EPO) may replace the lack of function of MPO is unknown. Eosinophil peroxidase is able to oxidise the same halides as MPO, but the oxidation of chloride by EPO is only possible at more acidic pH values [72], [295]. Human PMNs are able to bind and internalise EPO, whereby the enzyme is inactivated [296]

Conclusions

Myeloperoxidase is a Janus-faced-like enzyme that contributes to tissue injury in a number of pathologies, but is, on the other hand, involved in termination of inflammatory processes. Its functions are closely related to the fate of PMNs during inflammation.

Necrotic PMNs release large amount of MPO at inflammatory sites. Together with NO produced by upregulated iNOS, MPO-catalysed reactions contribute to an enhanced nitrosative stress. The further recruitment of PMNs is favoured by MPO

Acknowledgment

This work was supported by the German Research Foundation (Transregio 67, Project A-06).

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