The Dual Role of Myeloperoxidase in Immune Response

Abstract

The heme protein myeloperoxidase (MPO) is a major constituent of neutrophils. As a key mediator of the innate immune system, neutrophils are rapidly recruited to inflammatory sites, where they recognize, phagocytose, and inactivate foreign microorganisms. In the newly formed phagosomes, MPO is involved in the creation and maintenance of an alkaline milieu, which is optimal in combatting microbes. Myeloperoxidase is also a key component in neutrophil extracellular traps. These helpful properties are contrasted by the release of MPO and other neutrophil constituents from necrotic cells or as a result of frustrated phagocytosis. Although MPO is inactivated by the plasma protein ceruloplasmin, it can interact with negatively charged components of serum and the extracellular matrix. In cardiovascular diseases and many other disease scenarios, active MPO and MPO-modified targets are present in atherosclerotic lesions and other disease-specific locations. This implies an involvement of neutrophils, MPO, and other neutrophil products in pathogenesis mechanisms. This review critically reflects on the beneficial and harmful functions of MPO against the background of immune response.

Keywords: cardiovascular diseases; chronic inflammation; immune response; myeloperoxidase; neutrophils; phagosomes.

Figure 1

Major catalytic cycles of myeloperoxidase. Further explanations are given in the text. The heme states of MPO are denominated as in Table 1. X⁻ stands for Cl⁻, Br⁻, I⁻, and SCN⁻. HOX is the corresponding (pseudo)hypohalous acid. AH is an oxidizable substrate, and A^• the resulting substrate radical.

Figure 2

Major functions of granule constituents of PMNs in early phagosomes.