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Department of Infectious Medicine, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
Phagocyte-derived reactive oxygen species ("oxygen radicals") have been ascribed a suppressive role in immunoregulation by inducing dysfunction and apoptotic cell death in lymphocytes. Earlier studies show that human NK cells are exceptionally sensitive to oxygen radical-induced apoptosis and functional inhibition. Two subsets of human CD56+ NK cells have been identified: the highly cytotoxic CD56dim cells which constitute >90% of NK cells in peripheral blood, and the less cytotoxic but efficiently cytokine-producing CD56bright cells. In this study, we demonstrate that the CD56bright subset of NK cells, in contrast to CD56dim cells, remains viable and functionally intact after exposure to phagocyte-derived or exogenously added oxygen radicals. The resistance of CD56bright cells to oxidative stress was accompanied by a high capacity of neutralizing exogenous hydrogen peroxide, and by a high cell-surface expression of antioxidative thiols. Our results imply that CD56bright NK cells are endowed with an efficient antioxidative defense system that protects them from oxygen radical-induced inactivation.
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1 This work was supported by Swedish Cancer Society, Swedish Research Council, Inga-Britt and Arne Lundberg Research Foundation, and Sahlgrenska Academy at Göteborg University.
2 Address correspondence and reprint requests to Dr. Kristoffer Hellstrand, Department of Infectious Medicine, Sahlgrenska Academy at Göteborg University, Guldhedsgatan 10b, S-413 46 Göteborg, Sweden. E-mail address: kristoffer.hellstrand{at}microbio.gu.se
3 Abbreviations used in this paper: PMN, polymorphonuclear phagocyte; MP, mononuclear phagocyte; MFI, median fluorescence intensity; ALM-633, Alexa-633 C5-maleimide; PARP, poly(ADP-ribose)polymerase; AIF, apoptosis-inducing factor.
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