Induction of histamine release and densensitization in human leukocytes.

Protein A from Staphylococcus aureus has been found to react with all human leukocyte preparations tested. In 70 percent of the experiments the reaction leads to histamine release. Furthermore, protein A treatment of cells at 37 degrees C, both in complete and Ca-2+-free medium, results in the inhibition of anti-IgE-induced histamine release in all cell preparations, indicating that protein A and anti-IgE antibodies release histamine from the same cells. This inhibition seems to be due to the blocking or exhaustion of a step in the biochemical pathway, leading to histamine release activated by both protein A and anti-IgE. In some cell preparations desensitization but no histamine liberation is induced by protein A. No inhibition occurs if the protein A treatment is performed at 4 degrees C. It is concluded that protein A elicits histamine liberation and desensitization by acting on IgG present on the surface of the basophil granulocytes. Treatment of leukocytes at 37 degrees C with anti-IgE antibodies, or F(ab)2 fragments from such antibodies, also results in an inhibition of a subsequent anti-IgE-induced histamine release. Desensitization with low doses of anti-IgE results in an inhibition of the same type as that obtained with protein A. Supraoptimum amounts of anti-IgE or high amounts of monovalent Fab fragments from anti-IgE immunoglobulin G give an inhibition that could be due to a competition between the sensitizing and the challenging agents for combining with cell fixed IgE molecules. This inhibition is independent of temperature and calcium concentration.