Human eosinophils induce histamine release from antigen-activated rat peritoneal mast cells: A possible role for mast cells in late-phase allergic reactions

Background: Mast cells and eosinophils are believed to interact during the late and the chronic stages of allergic inflammation. Objective: In this study we investigated whether eosinophils can cause activation and consequent histamine release of already challenged mast cells, a situation likely to take place during the allergic late-phase reaction. Methods: Rat peritoneal mast cells presensitized with IgE antidinitrophenol-human serum albumin and challenged by dinitrophenol-human serum albumin or compound 48/80 were incubated with either eosinophil sonicate or major basic protein (MBP). Eosinophils were purified from the peripheral (>98%) blood of mildly allergic patients. Heparin and pertussis toxin and different extracellular Ca²⁺ concentrations were used to modulate mast cell reactivation by MBP. Histamine release was assessed as a marker of mast cell activation. Results: IgE-challenged mast cells were sensitive to reactivation induced by eosinophil sonicate and MBP. Reactivation was not cytotoxic for the mast cells. Mast cells previously challenged with compound 48/80 did not respond to subsequent MBP activation. Furthermore, heparin and pertussis toxin both inhibited mast cell reactivation induced by MBP. The ability of eosinophil sonicate and MBP to activate mast cells was not significantly affected at the different Ca²⁺ concentrations. Conclusions: In summary, we have shown a direct activating activity of eosinophils, partially due to MBP, toward IgE-challenged and immunologically desensitized mast cells. This suggests that in vivo mast cells can be reactivated during a late-phase reaction to release histamine by a non-IgE-dependent mechanism.