FREE-RADICAL FORMATION FROM ORGANIC HYDROPEROXIDES IN ISOLATED HUMAN POLYMORPHONUCLEAR NEUTROPHILS

被引:21
作者
CHAMULITRAT, W
COHEN, MS
MASON, RP
机构
[1] National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709
[2] Department of Medicine, Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill
关键词
ORGANIC HYDROPEROXIDES; MYELOPEROXIDASE; HUMAN POLYMORPHONUCLEAR NEUTROPHILS; FREE RADICALS; SPIN TRAPPING;
D O I
10.1016/0891-5849(91)90059-C
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have demonstrated with electron paramagnetic resonance (EPR) that organic hydroperoxides are decomposed to free radicals by both human polymorphonuclear leukocytes (PMNs) and purified myeloperoxidase. When tert-butyl hydroperoxide was incubated with either PMNs or purified myeloperoxidase, peroxyl, alkoxyl, and alkyl radicals were trapped by the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). In the case of ethyl hydroperoxide, DMPO radical adducts of peroxyl and alkyl (identified as alpha-hydroxyethyl when trapped by tert-nitrosobutane) radicals were detected. Radical adduct formation was inhibited when azide was added to the incubation mixture. Myeloperoxidase-deficient PMNs produced DMPO radical adduct intensities at only about 20-30% of that of normal PMNs. Our studies suggest that myeloperoxidase in PMNs is primarily responsible for the decomposition of organic hydroperoxides to free radicals. The finding of the free radical formation derived from organic hydroperoxides by PMNs may be related to the cytotoxicity of this class of compounds.
引用
收藏
页码:439 / 445
页数:7
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共 36 条
  • [1] Klebanoff, Clark, Anti-microbial systems, The neutrophil: Function and clinical disorders, pp. 409-488, (1978)
  • [2] Root, Cohen, The microbicidal mechanisms of human neutrophils and eosinophils, Rev. Infect. Dis., 3, pp. 565-598, (1981)
  • [3] Harrison, Schultz, Studies on the chlorinating activity of myeloperoxidase, J. Biol. Chem., 251, pp. 1371-1374, (1976)
  • [4] Birnboim, DNA strand breakage in human leukocytes exposed to a tumor promoter, phorbol myristate acetate, Science, 215, pp. 1247-1249, (1982)
  • [5] Weitberg, Weitzman, Destrempes, Latt, Stossel, Stimulated human phagocytes produce cytogenetic changes in cultured mammalian cells, New Engl. J. Med., 308, pp. 26-30, (1983)
  • [6] Sepe, Clark, Oxidant membrane injury by the neutrophil myeloperoxidase system, J. Immun., 134, pp. 1888-1895, (1985)
  • [7] Carlin, Djursater, Peroxidation of phospholipids promoted by myeloperoxidase, Free Rad. Res. Comms., 4, pp. 251-257, (1988)
  • [8] Odajima, Yamazaki, Myeloperoxidase of the leukocyte of normal blood I. Reaction of myeloperoxidase with hydrogen peroxide, Biochim. Biophys. Acta, 206, pp. 71-77, (1970)
  • [9] Rao, Flitter, Mason, The formation of free radical metabolites by mammalian peroxidases, Cellular antioxidant defense mechanisms, 1, pp. 59-71, (1988)
  • [10] Kalyanaraman, Sohnle, Generation of free radical intermediates from foreign compounds by neutrophil-derived oxidants, J. Clin. Invest., 75, pp. 1618-1622, (1985)