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HIGH acidity may be the trigger that clears a path for immune cells to reach damaged tissue, according to researchers in Israel. The enzyme heparanase, which allows these cells to invade tissues, seems to be activated only in acidic environments such as those found in areas of inflammation.

T lymphocytes, immune cells which circulate in the blood, must migrate across the walls of blood vessels in order to reach inflamed tissue. Much is known about how these cells pass through vascular walls, but the controls that operate once they get to the other side are less well understood.

When T cells encounter specific antigens, molecules which provoke an immune response, they start to produce large amounts of heparanase. This enzyme breaks down heparan sulphate, a major component of the dense complex substance known as the “extracellular matrix” that binds and stabilises tissues and blood vessels. This allows the T cells to penetrate the matrix and reach sites of inflammation.

Now it appears that the action of the enzyme is “switched” on and off depending on the pH of tissues. Dalia Gilat at the Weizmann Institute of Science in Rehovot, working with colleagues there and at Hadassah-Hebrew University Hospital in Jerusalem, found that heparanase functions as an enzyme only at low pH levels (Journal of Experimental Medicine, vol 181, p 1929). Acidic conditions are found in inflamed tissue and in growing tumours that are beginning to spread to other sites in the body. The pH in these tissues is around 6.8 because oxygen levels are low, causing carbon dioxide and lactic acid to accumulate.

At the higher pH of normal tissues (around 7.2), however, heparanase was found to function in an entirely different way. It binds to heparan sulphate without degrading it, and also binds to proteins on the surfaces of T cells. This anchors T cells in the extracellular matrix, stopping them invading normal tissue.