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Mast cells are major effectors of allergic responses, including to medications. Although often thought of as activated by IgE antibodies, mast cells can also be triggered by a variety of cationic compounds, termed basic secretagogues, which include inflammatory peptides and drugs. One of the mast cell receptors for these secretagogues is MRGPRX2.
McNeil et al. have now forged a path forward by identifying and studying the mouse ortholog of MRGPRX2 that is expressed in mast cells. Mrgprb2 was knocked out in mice that were then exposed to peptidergic drugs, such as leuprolide and octreotide, that are typically injected subcutaneously and cause local site reactions. Mice lacking Mrgprb2 did not exhibit paw swelling or mast cell–dependent histam…