Evaluation of the Effects of Chitin and Chitosan on Pseudo‐Allergic Reaction by Inhibiting <scp>MRGPRX2</scp> Activation

Chitin and chitosan, characterized by their extensive applications, abundant availability, and low cost, have been demonstrated to modulate immune responses. Mast cells (MCs) are important innate immune cells, and few studies on the regulation of MCs by chitin and chitosan were conducted. The key receptor Mas-related G protein-coupled receptor X2 (MRGPRX2), highly expressed in MCs, is involved in drug pseudo-allergic responses and several chronic diseases by mediating MC activation. However, the inhibitory effects of chitin and chitosan on MRGPRX2 activation of MCs have not been reported. To verify whether chitin and chitosan inhibit MRGPRX2-mediated MCs activation and determine which of these compounds shows the best inhibitory effect, in vitro MC degranulation reaction and in vivo substance P (SP)-induced local passive anaphylaxis models were used to evaluate the inhibitory effect of chitin and chitosan on MRGPRX2 activation of MCs. We showed that both chitin and chitosan inhibited MC degranulation mediated by MRGPRX2 and reduced β-hexosaminidase, histamine, TNF-α, MCP-1, and IL-8 release in vitro. Chitin and chitosan inhibit local pseudo-allergic reactions and reduce microvascular dilation by inhibiting MRGPRX2-mediated MC activation. Both chitin and chitosan inhibited MRGPRX2-mediated MC degranulation. However, chitosan showed a stronger inhibitory effect. Chitosan has the potential to be incorporated into functional foods as an auxiliary in the treatment of MRGPRX2-mediated chronic diseases.