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P10
P9
POSITIVES AND NEGATIVES OF OXIDANT FORMATION BY NEUTROPHILS Christine Winterbourn, University of Otago Christchurch, New Zealand Neutrophils are a major biological source of superoxide, hydrogen peroxide and myeloperoxidase-derived oxidants including hypohalous acids and free radicals. Reactive oxidants plays a vital role in their antimicrobial activity but can have detrimental effects when released from neutrophils that accumulate at sites of inflammation. Microbicidal activity is mostly confined to phagosomes, where large amounts of superoxide and hydrogen peroxide, along with myeloperoxidase, are released into the very small space surrounding the ingested organism. We have shown using fluorescent probes and specific biomarkers that hypochlorous acid (HOCl) is produced in the phagosome and reacts with both host and bacterial proteins. We have also seen upregulation of a transcription factor in phagocytosed bacteria that responds specifically to reactive chlorine species. Although HOCl is an important biocide, there is still uncertainty about the mechanism of oxidative killing and the roles of myeloperoxidase and HOCl. This conundrum will be discussed, along with emerging evidence that neutrophils generate oxidants for regulatory functions in addition to microbicidal activity.
Christine Winterbourn
doi: 10.1016/j.freeradbiomed.2016.10.025
P10
NEUTROPHIL EXTRACELLULAR TRAPS Arturo Zychlinsky, Max Planck Institute for Infection Biology, Germany Neutrophils are one of the first lines of defence of the immune system against microbes. These cells kill microorganisms effectively by phagocytosis and by the formation of extracellular structures, called Neutrophil Extracellular Traps (NETs). NETs are made of chromatin and specific neutrophil proteins and are released after a unique cell death program that requires the production of radical oxygen species (ROS) and the relocation of neutrophil elastase to the nucleus. NETs help limit and control infection and also can activate the acquired immune system. Thus, formation of NETs appears to be necessary for an efficient clearing of microbes but can also initiate and exacerbate autoimmune responses. doi: 10.1016/j.freeradbiomed.2016.10.026
Arturo Zychlinsky
S7
POSITIVES AND NEGATIVES OF OXIDANT FORMATION BY NEUTROPHILS Christine Winterbourn, University of Otago Christchurch, New Zealand Neutrophils are a major biological source of superoxide, hydrogen peroxide and myeloperoxidase-derived oxidants including hypohalous acids and free radicals. Reactive oxidants plays a vital role in their antimicrobial activity but can have detrimental effects when released from neutrophils that accumulate at sites of inflammation. Microbicidal activity is mostly confined to phagosomes, where large amounts of superoxide and hydrogen peroxide, along with myeloperoxidase, are released into the very small space surrounding the ingested organism. We have shown using fluorescent probes and specific biomarkers that hypochlorous acid (HOCl) is produced in the phagosome and reacts with both host and bacterial proteins. We have also seen upregulation of a transcription factor in phagocytosed bacteria that responds specifically to reactive chlorine species. Although HOCl is an important biocide, there is still uncertainty about the mechanism of oxidative killing and the roles of myeloperoxidase and HOCl. This conundrum will be discussed, along with emerging evidence that neutrophils generate oxidants for regulatory functions in addition to microbicidal activity.
Christine Winterbourn
doi: 10.1016/j.freeradbiomed.2016.10.025
P10
NEUTROPHIL EXTRACELLULAR TRAPS Arturo Zychlinsky, Max Planck Institute for Infection Biology, Germany Neutrophils are one of the first lines of defence of the immune system against microbes. These cells kill microorganisms effectively by phagocytosis and by the formation of extracellular structures, called Neutrophil Extracellular Traps (NETs). NETs are made of chromatin and specific neutrophil proteins and are released after a unique cell death program that requires the production of radical oxygen species (ROS) and the relocation of neutrophil elastase to the nucleus. NETs help limit and control infection and also can activate the acquired immune system. Thus, formation of NETs appears to be necessary for an efficient clearing of microbes but can also initiate and exacerbate autoimmune responses. doi: 10.1016/j.freeradbiomed.2016.10.026
Arturo Zychlinsky
S7