Evaluation of the inhibitory effect of different molecular weights chitosan on MRGPRX2-mediated mast cell degranulation and the pseudo-allergic reaction.

AbstractObjectivesMethodsKey findingsConclusionsChitosan is widely used in medicine to regulate immune responses in T cells and dendritic cells. However, research on the regulation of mast cells (MCs) is scarce. Mas-related G-protein-coupled receptor X2 (MRGPRX2) is a key receptor that mediates MC activation. However, the inhibitory effects of chitosan on MRGPRX2 activation have not yet been reported. The aim of this study was to determine whether chitosan inhibits MRGPRX2-mediated MC activation and the molecular weight of chitosan with the best inhibitory effect.Cytotoxic and activating effects of chitosan on LAD2 cells were evaluated <italic>in vitro</italic>. An <italic>in vitro</italic> MC degranulation reaction model and <italic>in vivo</italic> C48/80-induced local passive anaphylaxis mouse model were used to evaluate the inhibitory effect of chitosan on MRGPRX2 activation.Chitosan inhibited MC degranulation mediated by MRGPRX2 <italic>in vitro</italic> and reduced histamine, β-hexosaminidase, and cytokine release. Chitosan inhibited local pseudo-allergy and inflammatory mediator release by inhibiting MRGPRX2-mediated MC activation. Moreover, low-molecular-weight chitosan exhibited superior inhibitory activity against MRGPRX2.Chitosan inhibited MRGPRX2-mediated MC degranulation <italic>in vivo</italic> and <italic>in vitro</italic>. Low molecular weight chitosan has the potential to be developed as a functional drug or food to assist in the treatment of MRGPRX2-regulated diseases. [ABSTRACT FROM AUTHOR]