IgE-mediated histamine release from human basophils: differences between antigen E- and anti-IgE-induced secretion

Abstract

The mechanism of the IgE-mediated release of histamine from human basophils differs when the process is initiated by antigen as compared to anti-IgE (a-IgE). Antigen causes release from the basophils of different individuals over a wide range of concentrations, while release to a-IgE occurs over a limited concentration range; antigen excess inhibition is also relatively slight as compared to that observed with a-IgE. Release by antigen occurs with a shorter lag period and a more rapid rate than seen with a-IgE. Agonists which inhibit release by acting through adenylate cyclase (dimaprit, adenosine, isoproterenol) are significantly more potent with respect to antigen than to a-IgE-induced release. Other agonists (3-isobutyl-1-methylxanthine, dibutyryl cyclic AMP) which increase cyclic AMP by different mechanisms are equally effective against antigen and a-IgE, suggesting that the receptor-adenylate cyclase interactions differ between the two stimuli. The cyclooxygenase inhibitor, indomethacin, consistently enhances antigen- but not a-IgE-induced release while cytochalasin B, which acts in part on microfilaments, enhances both processes equally. These data indicate that cross-linking of surface antibody IgE by antigen initiates a release process different from that caused by a-IgE, perhaps because the former is a multivalent ligand and the latter is functionally bivalent.