Associate Professor Tony kettle and Professor Christine Winterbourn
"This issue has attracted a lot of debate over recent years," says Associate Professor Tony Kettle, "as it's an important area of research in understanding how humans fight infections.
"But it also sheds light on how our bodies are damaged during inflammatory diseases like cystic fibrosis, when white blood cells cause lung tissue deterioration through the production of bleach."
Led by Kettle and Professor Christine Winterbourn, the Free Radical Research Group's findings have recently been published in two leading journals - Biochemistry and The Journal of Biological Chemistry.
The key question up to now has focused on how white blood cells use oxygen to kill bacteria. It has been established for some time that these white cells, or neutrophils, process large amounts of oxygen when they surround and trap bacteria into special compartments.
Initially it was thought that the white cells converted oxygen to hydrogen peroxide and that was then used to kill the ingested bacteria in the cell. Later it was shown that some of the hydrogen peroxide was converted to bleach.
But now the Free Radical Group, in collaboration with colleagues at Auckland University, have produced clear and compelling evidence that bleach is the main antimicrobial agent produced from oxygen.
This finding has been achieved through detailed chemical experiments which examined how a major neutrophil enzyme uses reactive oxygen species to oxidise chloride to chlorine bleach.
Computer modelling of 30 chemical reactions demonstrated that when white blood cells ingest bacteria, the majority of the oxygen consumed is converted to chlorine bleach.
"The bleach is created within the cell compartments where bacteria are trapped and then destroyed. We've also shown that if cells lack the enzyme to make the bleach they kill bacteria much more slowly," explains Kettle.
Clarifying and demonstrating this process will lead to a better appreciation of how our immune systems fight infections. This knowledge may be crucial to future advances in antimicrobial therapies when bacteria become resistant to current antibiotics, as is the case with the rise of superbugs like MRSA.
Paradoxically, it will also help medical science better treat some inflammatory diseases, such as cystic fibrosis, in which bleach from overactive white blood cells damages vital organs.
FUNDING
Health Research Council