Formation of reactive sulfite-derived free radicals by the activation of human neutrophils: An ESR study

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• 作者：Kalina Ranguelova^a ; ¹ ; Annette B. Rice^b ; Abdelahad Khajo^c ; ^d ; Mathilde Triquigneaux^a ; Stavros Garantziotis^b ; Richard S. Magliozzo^c ; ^d ; Ronald P. Mason^a ; ^{mason4@niehs.nih.gov}
• 关键词：Sulfite toxicity ; Sulfite-derived radicals ; ESR spectroscopy ; DMPO ; Human neutrophils ; Myeloperoxidase ; Free radicals
• 刊名：Free Radical Biology and Medicine
• 出版年：2012
• 期刊代码：105_08915849
• 类别：med
• 出版时间：15 April, 2012
• 卷：52
• 期：8
• 页码：1264-1271
• 文件大小：721 K

摘要

The objective of this study was to determine the effect of (bi)sulfite (hydrated sulfur dioxide) on human neutrophils and the ability of these immune cells to produce reactive free radicals due to (bi)sulfite oxidation. Myeloperoxidase (MPO) is an abundant heme protein in neutrophils that catalyzes the formation of cytotoxic oxidants implicated in asthma and inflammatory disorders. In this study sulfite (^{鈥?/sup>SO₃鈭?/sup>) and sulfate (SO₄鈥⑩垝) anion radicals are characterized with the ESR spin-trapping technique using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) in the reaction of (bi)sulfite oxidation by human MPO and human neutrophils via sulfite radical chain reaction chemistry. After treatment with (bi)sulfite, phorbol 12-myristate 13-acetate-stimulated neutrophils produced DMPO-sulfite anion radical, -superoxide, and -hydroxyl radical adducts. The last adduct probably resulted, in part, from the conversion of DMPO-sulfate to DMPO-hydroxyl radical adduct via a nucleophilic substitution reaction of the radical adduct. This anion radical (SO₄鈥⑩垝) is highly reactive and, presumably, can oxidize target proteins to protein radicals, thereby initiating protein oxidation. Therefore, we propose that the potential toxicity of (bi)sulfite during pulmonary inflammation or lung-associated diseases such as asthma may be related to free radical formation.}