Myeloperoxidase, a Leukocyte-Derived Vascular NO Oxidase

Abstract

Myeloperoxidase (MPO) is an abundant mammalian phagocyte hemoprotein thought to primarily mediate host defense reactions. Although its microbicidal functions are well established in vitro, humans deficient in MPO are not at unusual risk of infection. MPO was observed herein to modulate the vascular signaling and vasodilatory functions of nitric oxide (NO) during acute inflammation. After leukocyte degranulation, MPO localized in and around vascular endothelial cells in a rodent model of acute endotoxemia and impaired endothelium-dependent relaxant responses, to which MPO-deficient mice were resistant. Altered vascular responsiveness was due to catalytic consumption of NO by substrate radicals generated by MPO. Thus MPO can directly modulate vascular inflammatory responses by regulating NO bioavailability.

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

“…MPO can oxidize NO, thereby inhibiting NO-dependent signaling and modulating reduction-oxidation-sensitive signaling cascades during inflammation. 14,57 One possible explanation for our findings is that MPO-deficient glial cells inappropriately regulate ROS and reactive nitrogen species under rotenone-exposed conditions, perhaps because of increased NO bioavailability (Figures 8 and 9). Several lines of evidences indicate that MPO may be a metabolic "sink" for several types of ROS, including superoxide and H 2 O 2 , and may, therefore, compromise NO bioavailability.…”

“…Increased MPO levels are widely considered characteristic of systemic inflammatory diseases. Recently, several interesting reports 13,14 have revealed that MPO has catalytic activity and exhibits cytokine-like properties, activating and modulating inflammatory signaling cascades. MPO has been closely involved in stimulating mitogen-activated protein kinase activity, cell growth, and protease activity, thereby influencing the immune responses and the progression of several inflammation-associated diseases.…”

Expression of myeloperoxidase enhances the chemosensitivity of leukemia cells through the generation of reactive oxygen species and the nitration of protein

“…It seemed that the ROS generated by MPO were involved in the nitration of tyrosine residues as reported previously. [17][18][19] Clinical observation has repeatedly shown a significant impact of the percentage of MPO-positive blasts on the prognosis of AML patients. [3][4][5] From data in this study, we postulate that MPO itself could enhance the cytotoxicity of chemotherapeutic agents through the generation of ROS or the nitration of cellular proteins, and that it could contribute, at least in part, to favorable responses to chemotherapy.…”

Mechanisms of H2O2-induced oxidative stress in endothelial cells

“…HOCl is formed via myloperoxidase in circulation and vascular cells and is associated with macrophage oxidation of LDL (Eiserich et al 2002). Myeloperoxidase is also heavily expressed in macrophages and other immune cells (Carr et al 2000b).…”