Many animal venoms contain factors that are able to trigger mast cell degranulation. In the Journal of Clinical Investigation, Galli and colleagues demonstrate that degranulation is critical for mitigating envenomation. The venom of the lizard Heloderma suspectum (the Gila monster) contains helodermin, a venom structurally similar to mammalian vasoactive intestinal peptide (VIP)—an important trigger of mast cell degranulation. Helodermin also triggers mast cell degranulation and is responsible for the symptoms of envenomation. Using mast cell–deficient mice and by mast cell grafting, the authors show that these cells are critical for protection against helodermin through their specific action at the site of venom challenge. Protection is mediated by the mast cell factor MCPT4, which degrades both helodermin and VIP, suggesting that MCPT4 is important in controlling not only venom toxicity but also physiological regulation of endogenous VIP.

J. Clin. Invest. 121, 4180–4191 (2011)