Given that tendency to overreact when stimulated by allergens, it seemed plausible that introducing venom into the body would trigger a similar response. But Galli and Martin Metz, MD, a postdoctoral scholar in pathology and first author of the study, have shown that when mast cells respond to selected venoms, they unleash proteins that break down some of the venoms' most toxic components.

The study was inspired by a 2004 paper in Nature, by Galli and a team of researchers including Metz, showing that mast cells reduced the mortality rate of mice suffering from bacterial peritonitis, a severe bacterial infection in the abdominal cavity that can also be fatal to humans. They found that mast cells released proteins that broke down a molecule called endothelin-1, one of the major toxins produced by the body during bacterial peritonitis or sepsis (bacterial infection in the blood).

In perusing the scientific literature, Metz noticed that endothelin-1 bore a striking similarity to sarafotoxin 6b, the most toxic component in the venom of the burrowing asp, or Israeli mole viper. Knowing also that mammalian mast cells had been shown to respond to many snake venoms by secreting some potent biologically active mediators, they hypothesized that mast cells might also act to degrade sarafotoxins and reduce the toxicity of the Israeli mole viper venom.

Galli and Metz first did experiments in vitro using isolated sarafotoxin 6b with mast cells from mice. "It worked as we thought it would," said Metz. The mast cells were activated, they released the expected proteins and the proteins degraded the sarafotoxin 6b. Mast cells also enhanced resistance of mice to sarafotoxin 6b when it was injected in vivo.

Next, Galli and Metz did experiments using the whole venom, not just the isolated toxin. Some of the mice they worked wi
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Contact: Louis Bergeron
louisb3@stanford.edu
650-725-2106
Stanford University Medical Center
27-Jul-2006