title: Reactive Oxygen Species and Neutrophil Function.
abstract: Neutrophils are essential for killing bacteria and other microorganisms, and they also have a significant role in regulating the inflammatory response. Stimulated neutrophils activate their NADPH oxidase (NOX2) to generate large amounts of superoxide, which acts as a precursor of hydrogen peroxide and other reactive oxygen species that are generated by their heme enzyme myeloperoxidase. When neutrophils engulf bacteria they enclose them in small vesicles (phagosomes) into which superoxide is released by activated NOX2 on the internalized neutrophil membrane. The superoxide dismutates to hydrogen peroxide, which is used by myeloperoxidase to generate other oxidants, including the highly microbicidal species hypochlorous acid. NOX activation occurs at other sites in the cell, where it is considered to have a regulatory function. Neutrophils also release oxidants, which can modify extracellular targets and affect the function of neighboring cells. We discuss the identity and chemical properties of the specific oxidants produced by neutrophils in different situations, and what is known about oxidative mechanisms of microbial killing, inflammatory tissue damage, and signaling.
authors.affiliation: Centre for Free Radical Research, Department of Pathology, University of Otago, Christchurch 8011, New Zealand; email: christine.winterbourn@otago.ac.nz , tony.kettle@otago.ac.nz , mark.hampton@otago.ac.nz.
authors.forename: Christine C
authors.initials: CC
authors.lastname: Winterbourn
authors.affiliation: Centre for Free Radical Research, Department of Pathology, University of Otago, Christchurch 8011, New Zealand; email: christine.winterbourn@otago.ac.nz , tony.kettle@otago.ac.nz , mark.hampton@otago.ac.nz.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kettle
authors.affiliation: Centre for Free Radical Research, Department of Pathology, University of Otago, Christchurch 8011, New Zealand; email: christine.winterbourn@otago.ac.nz , tony.kettle@otago.ac.nz , mark.hampton@otago.ac.nz.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Hampton
mesh_terms: D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D002700:Chloramines / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D006861:Hydrogen Peroxide / Q000276:immunology / Q000378:metabolism*; D006997:Hypochlorous Acid / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000819:agonists / Q000235:genetics / Q000276:immunology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013481:Superoxides / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013861:Thiocyanates / Q000276:immunology / Q000378:metabolism*; D015054:Zymosan / Q000494:pharmacology
chemical_list: D002700:Chloramines; D008562:Membrane Glycoproteins; D013861:Thiocyanates; C517667:hypothiocyanous acid; D013481:Superoxides; D006997:Hypochlorous Acid; D015054:Zymosan; D006861:Hydrogen Peroxide; D009195:Peroxidase; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C030816:chloramine; D013755:Tetradecanoylphorbol Acetate
keywords: antimicrobial; cell death; chloramine; hydrogen peroxide; hypochlorous acid; hypothiocyanous acid; inflammation; myeloperoxidase; redox signaling; superoxide