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

First Author  Wang Y Year  2022
Journal  J Allergy Clin Immunol Volume  150
Issue  5 Pages  1228-1231.e5
PubMed ID  35561839 Mgi Jnum  J:335792
Mgi Id  MGI:7293947 Doi  10.1016/j.jaci.2022.04.028
Citation  Wang Y, et al. (2022) Dynamin-related protein 1 differentially regulates FcepsilonRI- and substance P-induced mast cell activation. J Allergy Clin Immunol
abstractText  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: Drp1(fl/fl)Mcpt5cre(+/-) mice and Drp1(fl/fl)Cpa3cre(+/-) mice. RESULTS: In mice, Drp1 depletion enhanced FcepsilonRI-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.
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