5-Hydroxymethylfurfural multimers induce pseudo-allergic reaction through Fc epsilon RI at high doses

Under acidic and high temperature conditions, 5-hydroxymethylfurfural (5-HMF) converted from sugar further produces dimers (Compound II) and trimers (Compound III). The polymers were less reported, and sensitization effect of them was reported in this study. Compounds II and III induced the local and systemic anaphylaxis effect in passive cutaneous anaphylaxis mice model and activated RBL-2H3 cell inducing [Ca2+] mobilization, resulting in the release of beta-hexosaminidase and histamine in vitro. The gene knockdown assay figured out that Compounds II and III induced degranulation through Fc epsilon RI. Further, Compounds II and III had a certain affinity with Fc epsilon RI by cell membrane chromatography and may combine on the "proline sandwich " structure indicated by molecular docking. All above suggested Compounds II and III can induce pseudo-allergic reaction through Fc epsilon RI in vivo and in vitro. Our work provides basic research to prove that the newly discovered 5-HMF transformants, Compounds II and III, induce pseudo-allergic reaction in vitro and in vivo through Fc epsilon RI, which is different pathway from 5-HMF. In foods with high sugar content, the sensitization of Compounds II and III needs more attention. In high-sugar foods and medicines, especially traditional Chinese medicine injections, the content of transformants needs to be detected.