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

Abstract

The mitochondrial fission protein dynamin-related protein 1 (Drp1) has been suggested to regulate mast cell (MC) activation by certain stimuli invitro, but its functions in MCs activated by various stimuli invivo have not yet been examined. We sought to analyze Drp1 function in both mouse and human MCs. 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. In mice, Drp1 depletion enhanced FcεRI-induced MC activation while suppressing substance P-stimulated MC activation invitro and invivo. This was also true in human peripheral blood-derived cultured MCs invitro after pharmacologic inhibition of Drp1. 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.