Methods and Mechanisms of Mitigating Mast Cell Activation in Anaphylaxis

Abstract

A great number of people suffer from allergic disorders, some of which can be serious and life threatening. Unfortunately, there are limited ways to treat or prevent these maladies, in part due to our limited understanding. This dissertation addresses a novel mechanism of rapid desensitization, a procedure used to achieve temporary tolerance to allergens to prevent anaphylaxis, a severe allergic reaction involving mast cell degranulation. Specifically, we found that desensitization results in the aberrant reorganization of the actin cytoskeleton in mast cells, preventing calcium mobilization and inhibiting degranulation. Additionally, we found that a bacterial-derived phosphatase, YopH-TAT, could be potentially used for the treatment of allergic diseases, as it efficiently blocked mast cell activation by inhibiting tyrosine phosphorylation.