Myeloperoxidase: Regulation of Neutrophil Function and Target for Therapy

Abstract

Neutrophils, the most abundant white blood cells in humans, are critical for host defense against invading pathogens. Equipped with an array of antimicrobial molecules, neutrophils can eradicate bacteria and clear debris. Among the microbicide proteins is the heme protein myeloperoxidase (MPO), stored in the azurophilic granules, and catalyzes the formation of the chlorinating oxidant HOCl and other oxidants (HOSCN and HOBr). MPO is generally associated with killing trapped bacteria and inflicting collateral tissue damage to the host. However, the characterization of non-enzymatic functions of MPO suggests additional roles for this protein. Indeed, evolving evidence indicates that MPO can directly modulate the function and fate of neutrophils, thereby shaping immunity. These actions include MPO orchestration of neutrophil trafficking, activation, phagocytosis, lifespan, formation of extracellular traps, and MPO-triggered autoimmunity. This review scrutinizes the multifaceted roles of MPO in immunity, focusing on neutrophil-mediated host defense, tissue damage, repair, and autoimmunity. We also discuss novel therapeutic approaches to target MPO activity, expression, or MPO signaling for the treatment of inflammatory and autoimmune diseases.