Sugar to aid inflammation

Tuesday, 11 May, 2004

A discovery by United Kingdom Medical Research Council (MRC) scientists, working with colleagues at Oxford University, provides a promising platform for research into the development of new treatments for inflammatory diseases, including arthritis and asthma, and cancer.

The team has unravelled the structure and function of a common protein molecule at the heart of the process of inflammation. Reporting in the journal 'Molecular Cell', they reveal that certain sugar molecules that form part of a protein known as CD44 have a vital role to play in regulating whether or not inflammation occurs.

Scientists already knew that the protein, which is present in high numbers on the surface of white blood cells, is involved in the movement of these cells from the blood into body tissues during inflammation.

Normally, this is part of the body's immune response. It enables white blood cells to move to the site of an infection and attack bacteria and foreign particles. But, in the absence of proper regulation, it is also the cause of inflammatory diseases, such as arthritis and asthma. Furthermore, it can be the means by which cancer cells are able to break away from the primary tumour and spread around the body.

Although it was understood that CD44 allows cells to move out of the blood stream and into tissues by helping them attach to a sticky substance on the wall of blood vessels, called hyaluronan, it was not clear exactly how cells switch CD44 on and off.

Now, the research team, led by Dr David Jackson of the MRC's Human Immunology Unit, and Dr Tony Day of the MRC's Immunochemistry Unit, have discovered that the sugar molecules on the CD44 protein can actually block the site that binds with hyaluronan. It is the specific removal of these sugars that unblocks CD44, allowing cells to stick to hyaluronan and subsequently move into the tissues.

Dr Day said: "This exciting discovery should now make it possible to devise new strategies to prevent or reverse CD44 activation and this could have major therapeutic benefits for the treatment of inflammatory diseases and cancer. Work is now in progress to better understand how CD44 and hyaluronan fit together as the next step towards drug design."

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