Induction of histamine release and desensitization in human leukocytes

Histamine release from normal human leukocytes can be induced by anti-IgE or protein A from Staphylococcus aureus. After incubation in buffer at 37 degrees C for various time intervals or repeated washings with buffer, or both procedures, the leukocytes lose most of their reactivity to protein A, whereas the reactivity to anti-IgE is unaltered. Cells deprived of their protein A reactivity can be induced to release histamine by IgG complexed with protein A. Maximal release (23%-81%) from 0.6-1.0 times 10(7) leukocytes per ml is obtained if the mixture contains 1-2 mug protein A and 8-16 mug IgG per ml. The ratio between protein A and IgG in the most active mixtures is 1:8 or 1:16 on a weight basis, which corresponds to 2-4 IgG molecules per protein A molecule. Heat treatment does not destroy the capacity of IgG to mediate histamine release. Mixtures of protein A and the Fc part of IgG can also initiate the release. Futhermore, it is shown that the protein A-IgG mixture and anti-IgE induce cross-desensitization to each other. This indicates that, like cell-bound IgG, IgG in complex with protein A triggers partially the same reaction sequence as IgE.