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

Objectives: Chitosan 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.

Methods: Cytotoxic and activating effects of chitosan on LAD2 cells were evaluated in vitro. An in vitro MC degranulation reaction model and in vivo C48/80-induced local passive anaphylaxis mouse model were used to evaluate the inhibitory effect of chitosan on MRGPRX2 activation.

Key findings: Chitosan inhibited MC degranulation mediated by MRGPRX2 in vitro 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.

Conclusions: Chitosan inhibited MRGPRX2-mediated MC degranulation in vivo and in vitro. 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.