Mechanism of walnut induced anaphylaxis-like shock reaction in mice (175.1)

Abstract

Abstract Walnut is a leading cause of life-threatening anaphylaxis in humans. Such reactions are largely thought to be mediated by the Type-I hypersensitivity mechanism. We have found that English walnut extract (EWE) upon oral or i.p., administration in naive mice without pre-sensitization results in anaphylaxis-like shock response as quantified by hypothermia. We have been studying the mechanism underlying this unusual reaction. The Fcg receptor knockout (KO) mice, IgE non-responder SJL mice and TLR4 mutant C3H/HeJ mice, all exhibited hypothermia response indicating that the reaction was antibody and LPS independent respectively. We then examined the role of complement system. The C3a receptor (C3aR) KO mice were protected from shock responses. Among the C5 deficient (DBA/1J) and C5 sufficient (DBA/2J) mice, both exhibited hypothermia responses with DBA1 being a slightly lower responder. Since the shock reaction was complement dependent, we reasoned and tested whether EWE causes hemagglutination (HA) of RBC. Using a standard HA assay protocol we evaluated the HA activity of EWE. We found that the EWE had a significant HA activity for RBC obtained from BALB/c, DBA/1J and DBA/2J mice (HA titre: 1/32; translates to ~35,555 HA units per gram of EWE protein). These data are consistent with the hypothesis that EWE causes HA in vivo leading to complement system activation with consequent C3aR dependent anaphylaxis-like shock reaction.