Persistence of early crosslink-dependent signal transduction events in human basophils after desensitization.
Desensitization of human basophils with anti-IgE antibody or antigen induced an increased sensitivity to the phorbol ester TPA, evidenced as 2-5 fold increase in the potency of TPA to induce histamine release. As noted in previous publications the magnitude of the change in sensitivity to TPA was a function of the extent of cell surface IgE crosslinking. Thus, the density of cell surface antigen-specific IgE determined the magnitude of the curve shift and the multivalent antigen, BPO21-HSA was found to produce a greater curve shift than the simpler bivalent hapten, BPO2, in accord with previous studies which demonstrated that BPO2 was a "weak" stimulus compared to BPO21-HSA. Basophils which had been fully desensitized by prior treatment with anti-IgE or antigen in the absence of calcium also displayed the curve shift for at least 24 h after desensitization. However, the change induced by crosslinking which altered the cells' sensitivity to TPA required the continued presence of crosslinks and was therefore not the result of a permanent alteration induced by desensitization. Basophils which were fully desensitized to BPO7-HSA demonstrated the curve shift provided that the antigen-induced crosslinks were maintained: treatment with monovalent hapten, BPO-EACA, rapidly returned the cell response to TPA to control, non-desensitized, levels. Since TPA is thought to act by activation of protein kinase C (PKC) we demonstrated that BPO-HSA induced crosslinking increased PKC activity and that the increased activity persisted unless antigen-induced crosslinks were dissociated by the addition of monovalent hapten.(ABSTRACT TRUNCATED AT 250 WORDS)
Warner
J
J
Johns Hopkins University School of Medicine, Good Samaritan Hospital, Baltimore, Maryland 21236.
MacGlashan
D
D
D000936:Antigen-Antibody Complex; D001491:Basophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D066298:In Vitro Techniques; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D007073:Immunoglobulin E; D013755:Tetradecanoylphorbol Acetate