Proteases commit microbicide

White blood cells use proteases to kill their targets, according to new results from Emer Reeves, Hiu Lu, Anthony Segal (University College, London, England), and colleagues. The findings contradict previously accepted notions that reactive oxygen species (ROSs) are the killing agents.

ROSs like superoxide are produced by NADPH oxidase activity when white blood cells, primarily neutrophils, phagocytose pathogens. For decades it has been thought that high concentrations of the toxic ROSs resulting from this respiratory burst are directly responsible for killing microorganisms. But the new results prove otherwise.

Segal's group showed that mice deficient in protease activity have increased sensitivity to microbes. Additionally, purified neutrophils from the protease-deficient mice are impaired in their antimicrobial activity in vitro. “Our results are conclusive,” says Segal. “By taking out the proteases, we do not interfere with the respiratory burst, but...