During the inflammatory response — the first and most ancient line of immune defense — white blood cells migrate into damaged tissue. The microenvironment within these tissues is often oxygen-deficient, and hypoxia-inducible factor-1 (HIF-1) has been shown to be a key mediator of adaptation to such conditions. In the March 7 Cell, Randall Johnson and colleagues at the University of California at San Diego, US, show that absence of HIF-1 prevents white cell migration and activation, drastically inhibiting the inflammatory response, and it does so by inhibiting anaerobic production of ATP (Cell, 112:645-657, March 7, 2003).

Johnson et al. examined the effect of knocking out HIF-1 on the inflammatory response both in vitro and in mice. Loss of HIF-1 reduced ATP levels to 15-20% of hypoxic normal, completely prevented macrophage adhesion (a key step in tissue infiltration), and reduced infiltration into a gel matrix by 60%....

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