title: Sulfite-mediated oxidation of myeloperoxidase to a free radical: immuno-spin trapping detection in human neutrophils.
abstract: Previous studies focused on catalyzed oxidation of (bi)sulfite, leading to the formation of the reactive sulfur trioxide ((•)SO3(-)), peroxymonosulfate ((-)O3SOO(•)), and sulfate (SO4(•-)) anion radicals, which can damage target proteins and oxidize them to protein radicals. It is known that these very reactive sulfur- and oxygen-centered radicals can be formed by oxidation of (bi)sulfite by peroxidases. Myeloperoxidase (MPO), an abundant heme protein secreted from activated neutrophils that play a central role in host defense mechanisms, allergic reactions, and asthma, is a likely candidate for initiating the respiratory damage caused by sulfur dioxide. The objective of this study was to examine the oxidative damage caused by (bi)sulfite-derived free radicals in human neutrophils through formation of protein radicals. We used immuno-spin trapping and confocal microscopy to study the protein oxidations driven by sulfite-derived radicals. We found that the presence of sulfite can cause MPO-catalyzed oxidation of MPO to a protein radical in phorbol 12-myristate 13-acetate-activated human neutrophils. We trapped the MPO-derived radicals in situ using the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide and detected them immunologically as nitrone adducts in cells. Our present study demonstrates that myeloperoxidase initiates (bi)sulfite oxidation leading to MPO radical damage, possibly leading to (bi)sulfite-exacerbated allergic reactions.
authors: Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors: Kalina
authors: K
authors: Ranguelova
authors: Annette B
authors: AB
authors: Rice
authors: Olivier M
authors: OM
authors: Lardinois
authors: Mathilde
authors: M
authors: Triquigneaux
authors: Natacha
authors: N
authors: Steinckwich
authors: Leesa J
authors: LJ
authors: Deterding
authors: Stavros
authors: S
authors: Garantziotis
authors: Ronald P
authors: RP
authors: Mason
mesh_terms: D005609:Free Radicals / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism*; D010545:Peroxides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D010703:Phorbol Esters / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D019097:Spin Trapping; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D013447:Sulfites / Q000378:metabolism / Q000633:toxicity*; D013461:Sulfur Oxides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity
chemical_list: D005609:Free Radicals; D010545:Peroxides; D010703:Phorbol Esters; D011506:Proteins; D013431:Sulfates; D013447:Sulfites; D013461:Sulfur Oxides; C038288:peroxymonosulfate; C008874:phorbol-12,13-diacetate; D009195:Peroxidase; C011118:sulfur trioxide; C042345:hydrogen sulfite
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