th were genetically deficient in mast cells, while others, called wild-type mice, had normal mast cells. "We saw the same results in the wild-type mice that we saw before with just the one component, sarafotoxin 6b," said Metz. The mast cells were activated via a particular receptor they had on the cell surface and released the appropriate proteins, which, Metz said, went on to "degrade and thus eliminate the venom, or at least make it less toxic."

The wild-type mice were able to withstand 10 times the dosage of this venom than the mast cell deficient mice could, further indicating that the mast cells were reducing the impact of the venom. To test whether mast cells could also reduce the toxicity of venom from snakes that didn't contain toxins comparable to sarafotoxin 6b, Galli and Metz tested the venom of the western diamondback rattlesnake and the southern copperhead. Again, the mast cells conferred a distinct protective edge.

Testing the mast cell response even further, they also experimented with the venom from honeybees, with the same positive result. "The mast cells significantly limit not only the toxicity, but also the mortality associated with the venom," said Galli.

But Galli called the battle between predators with venom and their prey "a kind of evolutionary arms race." He and Metz suspect that, given the broad range of venoms that have been developed by snakes and other creatures, mast cells probably won't perform as well against every type of venom.

"We expect that there will be some snake venoms that either are not affected by mast cells at all or perhaps even elicit more pathology due to their ability to activate mast cells. It all depends on the balance between the positive and negative effects of the mediators released by mast cells in response to a particular venom," said Galli.

Galli and Metz are embarking on a systematic survey of animal venoms. As more is learned about the natural defenses the
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Contact: Louis Bergeron
louisb3@stanford.edu
650-725-2106
Stanford University Medical Center
27-Jul-2006

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