Dynamin-related protein 1 differentially regulates FcεRI- and substance P-induced mast cell activation

Background The mitochondrial fission protein dynamin-related protein 1 (Drp1) has been suggested to regulate mast cell (MC) activation by certain stimuli in vitro, but its functions in MCs activated by various stimuli in vivo have not yet been examined. Objective We sought to analyze Drp1 function in both mouse and human MCs. Methods We used human peripheral blood–derived cultured MCs and 2 genetic mouse models in which MCs were depleted of Drp1: Drp1fl/flMcpt5cre+/− mice and Drp1fl/flCpa3cre+/− mice. Results In mice, Drp1 depletion enhanced FcεRI-induced MC activation while suppressing substance P–stimulated MC activation in vitro and in vivo. This was also true in human peripheral blood–derived cultured MCs in vitro after pharmacologic inhibition of Drp1. Conclusion Drp1 differentially regulates MC activation by various stimuli. Promoting Drp1 activation might therefore represent a novel therapy for suppressing IgE-dependent MC activation. Further, inhibiting Drp1 activation might mitigate other MC-dependent responses, such as those induced by substance P.