TY - JOUR

T1 - Neutrophils and redox stress in the pathogenesis of autoimmune disease

AU - Glennon-Alty, Laurence

AU - Hackett, Angela P

AU - Chapman, Elinor A

AU - Wright, Helen L

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018/9

Y1 - 2018/9

N2 - Polymorphonuclear leukocytes, or neutrophils, are specialist phagocytic cells of the innate immune system. Their primary role is host defence against micro-organisms, which they kill via phagocytosis, followed by release of reactive oxygen species (ROS) and proteolytic enzymes within the phagosome. ROS are generated via the action of the NADPH oxidase (also known as NOX2), in a process termed the 'Respiratory Burst'. This process consumes large amounts of oxygen, which is converted into the highly-reactive superoxide radical O2- and H2O2. Subsequent activation of myeloperoxidase (MPO) generates secondary oxidants and chloroamines that are highly microbiocidal in nature, which together with proteases such as elastase and gelatinase provide a toxic intra-phagosomal environment able to kill a broad range of micro-organisms. However, under certain circumstances such as during an auto-immune response, neutrophils can be triggered to release ROS and proteases extracellularly causing damage to host tissues, modification of host proteins, lipids and DNA and dysregulation of oxidative homeostasis. This review describes the range of ROS species produced by human neutrophils with a focus on the implications of neutrophil redox products in autoimmune inflammation.

AB - Polymorphonuclear leukocytes, or neutrophils, are specialist phagocytic cells of the innate immune system. Their primary role is host defence against micro-organisms, which they kill via phagocytosis, followed by release of reactive oxygen species (ROS) and proteolytic enzymes within the phagosome. ROS are generated via the action of the NADPH oxidase (also known as NOX2), in a process termed the 'Respiratory Burst'. This process consumes large amounts of oxygen, which is converted into the highly-reactive superoxide radical O2- and H2O2. Subsequent activation of myeloperoxidase (MPO) generates secondary oxidants and chloroamines that are highly microbiocidal in nature, which together with proteases such as elastase and gelatinase provide a toxic intra-phagosomal environment able to kill a broad range of micro-organisms. However, under certain circumstances such as during an auto-immune response, neutrophils can be triggered to release ROS and proteases extracellularly causing damage to host tissues, modification of host proteins, lipids and DNA and dysregulation of oxidative homeostasis. This review describes the range of ROS species produced by human neutrophils with a focus on the implications of neutrophil redox products in autoimmune inflammation.

KW - Animals

KW - Autoimmune Diseases/etiology

KW - Humans

KW - Neutrophils/pathology

KW - Oxidation-Reduction

KW - Oxidative Stress

KW - Reactive Oxygen Species/metabolism

U2 - 10.1016/j.freeradbiomed.2018.03.049

DO - 10.1016/j.freeradbiomed.2018.03.049

M3 - Review article

C2 - 29605448

VL - 125

SP - 25

EP - 35

JO - Free radical biology & medicine

JF - Free radical biology & medicine

SN - 0891-5849

ER -