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Oxidative Stress in Health and Disease

53 months
Approved budget:
Professor Anthony Kettle
Health issue:
Other (generic health or health services)
Proposal type:
Programme Extension
Lay summary
Life thrives in an atmosphere of oxygen because cells use intricate strategies to exploit its exceptional chemistry while minimizing its toxicity. We contend that a deep understanding of how our bodies use oxygen will give insights into the etiology of many diseases. Our research is aimed at understanding how reactive forms of oxygen contribute to normal physiology and the sequelae of inflammation. We plan to investigate why they are essential for fighting infections but detrimental in numerous inflammatory diseases. We will also explore how cells respond to reactive forms of oxygen and regulate their production. There is a large emphasis on neutrophils and the reactive oxidants they generate in response to infection and inflammation. These phagocytic cells are the dominant white blood cell in circulation and are our primary defenders against invading pathogens [1]. Their production of reactive oxygen species, including superoxide and hydrogen peroxide, is essential for killing most bacteria. They also contain the green haem enzyme myeloperoxidase (MPO), which produces the strong oxidant chlorine bleach from hydrogen peroxide and chloride [2]. The reactive oxygen species generated by neutrophils are implicated in the tissue damage associated with numerous inflammatory diseases but hard evidence of their complicity in pathology is still lacking. Nevertheless, the continued support for the participation of MPO in cardiovascular disease (CVD) suggests that chlorine bleach and related oxidants do exacerbate inflammation in this and other inflammatory pathologies.