Impaired basophil histamine release from allergic patients.

A few patients (6-7%) with a verified type I allergic reaction do not respond with histamine release after challenge of their basophils with specific antigen (non-responding basophils from allergic patients). Sera from these non-responding patients were used for passive sensitization of responding cells from healthy controls. When these sensitized cells were challenged with specific antigen, histamine release was observed indicating that the non-responding allergic patients have circulating antigen-specific IgE capable of binding to Fc-receptors on the basophils. These findings suggest the possibility that non-responding basophils have impaired cell functions. We therefore examined the influence of enhanced IgE receptor stimulation on histamine release in non-responding basophils. This was made by stimulating protein kinase C activity by a phorbol ester (phorbol 12-myristate 13-acetate). When the non-responding cells were incubated with the phorbol ester and challenged with either anti-IgE or specific antigen, the cells released histamine. These findings support the hypothesis that the unresponsiveness of basophils in some allergic patients is associated with impaired IgE receptor complex activation or subcellular functioning and not with a lack of cell-bound IgE.