Hypochlorite- and hypobromite-mediated radical formation and its role in cell lysis
Hypochlorite- and hypobromite-mediated radical formation and its role in cell lysis
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DOI：
10.1006/abbi.2001.2581
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发表时间：
2001-11-15
影响因子：
3.9
通讯作者：
Davies, MJ
中科院分区：
文献类型：
--
作者：
Hawkins, CL;Brown, BE;Davies, MJ
活化的白细胞通过形成H2O2和释放过氧化物酶（髓过氧化物酶、嗜酸性粒细胞过氧化物酶）产生强效氧化剂HOCl和HOBr。HOCl和HOBr是有效的杀微生物剂，但过量或错位生产可引起组织损伤和细胞裂解。本研究表明，HOBr在比HOCl低约10倍的浓度下诱导红细胞溶解，而在单核细胞（THP1）和巨噬细胞（J774）中，HOCl和HOBr在相似的浓度下诱导红细胞溶解。通过EPR自旋捕获研究了自由基在裂解过程中形成的作用，结果表明，两种氧化剂与每种细胞类型的反应都会产生细胞源性自由基。暴露于非溶解剂量HOCl的红细胞产生新的氮中心自由基，其形成依赖于谷胱甘肽。相反，HOBr产生以氮为中心的膜源性蛋白自由基。在任何一种氧化剂的溶解剂量下，都可以观察到蛋白质（可能是血红蛋白）衍生的氮中心自由基。与红细胞不同，用HOCl治疗单核细胞和巨噬细胞只有在细胞溶解同时发生的情况下才会产生明显的自由基。这些自由基以氮为中心，来源于细胞蛋白，其参数与红细胞和HOBr检测到的自由基相同。将这些细胞暴露于HOBr中，没有检测到自由基。总的来说，这些实验表明HOCl和HOBr与细胞靶标的选择性不同，这可以导致自由基的形成。这种自由基的产生可以先于细胞裂解，并可能在细胞裂解中起作用。(C) 2001学术出版社。
Activated leukocytes generate the potent oxidants HOCl and HOBr via the formation of H2O2 and the release of peroxidase enzymes (myeloperoxidase, eosinophil peroxidase). HOCl and HOBr are potent microbiocidal agents, but excessive or misplaced production can cause tissue damage and cell lysis. In this study it is shown that HOBr induces red blood cell lysis at approximately 10-fold lower concentrations than HOCl, whereas with monocyte (THP1) and macrophage (J774) cells HOCl and HOBr induce lysis at similar concentrations. The role of radical formation during lysis has been investigated by EPR spin trapping, and it is shown that reaction of both oxidants with each cell type generates cell-derived radicals. Red blood cells exposed to nonlytic doses of HOCl generate novel nitrogen-centered radicals whose formation is GSH dependent. In contrast, HOBr gives rise to nitrogen-centered, membrane-derived protein radicals. With lytic doses of either oxidant, protein (probably hemoglobin)-derived, nitrogen-centered radicals are observed. Unlike the red blood cells, treatment of monocytes and macrophages with HOCl gives significant radical formation only under conditions where cell lysis occurs concurrently. These radicals are nitrogen-centered, cell-protein-derived species and have parameters identical to those detected with red blood cells and HOBr. Exposure of these cells to HOBr did not give detectable radicals. Overall these experiments demonstrate that HOCl and HOBr react with different selectivity with cellular targets, and that this can result in radical formation. This radical generation can precede, and may play a role in, cell lysis. (C) 2001 Academic Press.