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Without the mast cell protease Mc-cpa, most mice die within an hour of being injected with ET-1.
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High blood pressure, sepsis, and snake bites might all be cured by the same antidote, according to Schneider et al. (page 2629).
High blood pressure and septic shock are both enhanced by a 21–amino acid peptide called ET-1. This peptide is secreted by blood vessel cells that have been activated by inflammatory cytokines. ET-1 triggers the contraction of smooth muscle cells that are wrapped around blood vessels, causing blood to flow through the squeezed vessels at a higher pressure. This contraction prevents blood from getting to its target tissues, leading to sepsis-associated organ malfunction.
ET-1 is structurally similar to a snake venom toxin called sarafotoxin. This toxin is lethal to mice that lack a type of immune cell called mast cells. These mice also die when sepsis-causing bacteria enter the abdominal cavity from an injured gut.
How mast cells protect against sepsis and snake venom, however, was unclear. They express both ET-1 receptors and degradative enzymes that normally destroy pathogens. The authors thus imagined that the mast cells might trap ET-1 (and the toxin) and then degrade it. They focused on mast cells' most abundant defensive protease, Mc-cpa.
The team now shows that Mc-cpa is indeed the weapon of choice against ET-1 and the toxin. Mice that lack mast cells died within hours after injection with ET-1. Mc-cpa protected mice by snipping and thus disarming the dangerous peptides. Mice that secreted inactive Mc-cpa were as susceptible to sepsis and snake venom as mice that lacked mast cells.
ET-1 is needed for mast cell activation, but its subsequent degradation might limit its long-term destructive effects. 
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