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Discovery improves understanding of early onset inflammatory disease

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5 July 2012

Scientists at the University of East Anglia (UEA) funded by BBSRC have discovered a 'constant cloud' of potent inflammatory molecules surrounding the cells responsible for diseases such as thickening of the arteries and rheumatoid arthritis.

Published online today by The Journal of Cell Science, the findings could eventually lead to new treatments for chronic inflammatory diseases. Cardiovascular disease arising from atherosclerosis (thickening of the arteries) kills around 17 million people worldwide each year, including 120,000 people in England and Wales, while rheumatoid arthritis affects around 400,000 people in the UK.

A scanning electron microscope image of human blood showing red blood cells and several infection-fighting white blood cells including a monocyte. US National Cancer Institute/Bruce Wetzel/Harry Schaefer

A scanning electron microscope image of human blood showing red blood cells and several infection-fighting white blood cells including a monocyte. Image: US National Cancer Institute/Bruce Wetzel/Harry Schaefer

The UEA team studied a type of white blood cell called monocytes. Monocytes play an important role in the human immune system and help protect our bodies against infection. But they can also invade tissue, triggering the early stages of common inflammatory diseases.

The researchers detected for the first time that monocytes were surrounded by a constant cloud. This cloud was found to be made up of potent inflammatory molecules called adenosine triphosphate, or ATP. Further study showed that the ATP molecules were being propelled through the cell wall by the actions of lysosomes. Lysosomes are sub-cellular compartments within blood cells which had previously been thought to only break down cell waste.

"These unexpected findings shed light on the very early stages in the development of inflammatory diseases such as atherosclerosis and rheumatoid arthritis," said lead author Dr Samuel Fountain of UEA's School of Biological Sciences.

"We found that lysosomes are actually highly dynamic and play a key role in the way inflammatory cells function. This is an exciting development that we hope will lead to the discovery of new targets for inflammatory drugs in around five years and potential new treatments beyond that."

Dr Fountain said further study was now needed to investigate how to control the release of ATP by lysosomes in monocytes and other white blood cells, and to understand how inflammation may be affected in patients with inherited diseases involving lysosomes.

Dr Fountain is a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellow and recently received £0.9M from BBSRC to study how cells use ATP as a signalling molecule.

'Constitutive lysosome exocytosis releases ATP and engages P2Y receptors in human monocytes' by V Sivaramakrishnan (UEA), S Bidula (UEA), H Campwala (UEA), D Katikaneni (UEA) and S Fountain (UEA) is published online on July 5 by the Journal of Cell Science.

ENDS

Notes to editors

To arrange pictures or interviews please contact Simon Dunford at the UEA Communications Office: +44 (0)1603 592203 / 07827 082668 / s.dunford@uea.ac.uk

The paper is available on request - under embargo until 00:01 BST on Thursday July 5.

About the University of East Anglia

The University of East Anglia (UEA) is ranked in the top one per cent of universities in the world and is consistently in the top ten for student satisfaction. It is a leading member of the Norwich Research Park, one of Europe's biggest concentrations of researchers in the fields of environment, health and plant science.

UEA's School of Biological Sciences is ranked 14th in the Guardian League Table 2013 and 90 per cent of research activity was classified as internationally leading, excellent or recognised in the latest Research Assessment Exercise. The school also recorded a 100 per cent student satisfaction rate in the 2011 National Student Survey. www.uea.ac.uk/bio

About BBSRC

BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.

Funded by Government, and with an annual budget of around £445M (2011-2012), we support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.

For more information about BBSRC, our science and our impact see: www.bbsrc.ac.uk.
For more information about BBSRC strategically funded institutes see: www.bbsrc.ac.uk/institutes.