Their discovery, detailed in the March 7 issue of the journal Cell, could lead to the development of a new class of drugs for treating the debilitating and painful joint inflammation in the 43 million Americans who suffer from arthritis. It also may help doctors treat cancer more effectively, because tumor development is associated with a pronounced inflammatory response in the vast majority of cases.

Scientists had previously documented the mechanisms by which white blood cells are directed to sites of injury by the low oxygen levels typically found at those locations. "When you have a cut, the local vascular structure surrounding the wound is disrupted and there's no longer a normal supply of oxygen being delivered," says Randall S. Johnson, an associate professor of biology, who headed the study. "White blood cells (leukocytes) constitute the first line of defense against invading microorganisms like bacteria or viruses and accumulate at sites of injury. Because these cells operate outside of the blood vessels, they need to be able to function in a low-oxygen environment."

Leukocytes that enter these low oxygen, or hypoxic, environments also possess molecular and genetic "switches" that allow them to change their metabolism from an oxygen-dependent (aerobic) to an oxygen-independent (anaerobic) mode of generating energy. But until now, the importance of those switches to regulate inflammation was not well understood. By eliminating the ability of the white blood cells-specifically macrophages and neutrophils-to turn on their hypoxic response and generate energy anaerobically, the UCSD scientists were able to stop the usual developm
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Contact: Randall S. Johnson
rsjohnson@ucsd.edu
858 822-0509
University of California - San Diego
6-Mar-2003