Myeloperoxidase: A new player in autoimmunity

Abstract

Myeloperoxidase (MPO) is the most toxic enzyme found in the azurophilic granules of neutrophils. MPO utilizes H2O2 to generate hypochlorous acid (HClO) and other reactive moieties, which kill pathogens during infections. In contrast, in the setting of sterile inflammation, MPO and MPO-derived oxidants are thought to be pathogenic, promoting inflammation and causing tissue damage. In contrast, evidence also exists that MPO can limit the extent of immune responses. Elevated MPO levels and activity are observed in a number of autoimmune diseases including in the central nervous system (CNS) of multiple sclerosis (MS) and the joints of rheumatoid arthritis (RA) patients. A pathogenic role for MPO in driving autoimmune inflammation was demonstrated using mouse models. Mechanisms whereby MPO is thought to contribute to disease pathogenesis include tuning of adaptive immune responses and/or the induction of vascular permeability.

Protocatechuic acid inhibits testicular and epididymal toxicity associated with methotrexate in rats

“…TNF‐α reportedly leads and controls cytokine flow throughout an inflammatory reaction as well as up‐regulates inducible nitric oxide (iNOS) synthase boosting NO production (Chen, Zhou, Gao, & Jiang, ). Further, persistent inflammation reportedly stimulates MPO produces noxious hypochlorite and ROS which subsequently worsens oxidative damage (Strzepa, Pritchard, & Dittel, ) (Lu, Sui, Tian, & Peng, ). Thus, reduction in the MPO activity, IL‐1β, NO and TNF‐α levels in epididymis and testes of rats indicates an anti‐inflammatory mechanism of PCA in abating MTX‐mediated toxicity.…”

Saliva and serum biomarkers in periodontitis and coronary artery disease

“…Thirdly, myeloperoxidase (MPO) associates with inflammation (Leppilahti et al., ), activating oxidatively latent MMP‐8 and MMP‐9 and inactivating TIMP‐1 (Saari, Suomalainen, Lindy, Konttinen, & Sorsa, ). MPO kills bacteria also by generating reactive oxygen species, that is hypochlorous acid (Strzepa, Pritchard, & Dittel, ).…”

OX40 expression in neutrophils promotes hepatic ischemia/reperfusion injury

“…Meanwhile, the expression of Nox2 and Mpo was decreased in the Ox40-deficient neutrophils. Because the NOX2/MPO axis is critical for oxidative burst in neutrophils, which is relevant to redundant reactive oxidant generation and tissue damage (28,29), we speculate that OX40 may be involved in oxidant generation and subsequent oxidative stress in neutrophils.…”