Professor Tony Kettle

Research

Professor Kettle is a principal investigator in the Centre for Free Radical Research (CFRR) at the University of Otago, Christchurch. His research is focused on the enzymology of the haem enzyme myeloperoxidase and its impact of host defense and inflammatory tissue damage. This protein is responsible for the green tinge in pus and phlegm. It catalyzes the production of chlorine bleach from hydrogen peroxide and common salt.

The work of the CFRR has advanced the understanding of how the enzyme contributes to bacterial killing by white blood cells known as neutrophils. We have also demonstrated how hypohalous acids and free radicals are produced during inflammation and cause tissue damage. In clinical investigations we showed that chlorine bleach damages tissues during inflammation in rheumatoid arthritis, cystic fibrosis, asthma and cardiovascular disease. In collaboration with AstraZeneca, we identified potent inhibitors of myeloperoxidase that have potential as anti-inflammatory drugs.

In more recent work, we have shown that urate is a physiological substrate for myeloperoxidase. The enzyme uses hydrogen peroxide to oxidize urate to reactive electrophiles that propagate oxidative stress during inflammation by forming adducts with amine groups on proteins.