Differential inhibition of histamine release from human basophils induced by antigen, anti-IgE or N-formyl-L-methionyl-L-leucyl-L-phenylalanine.

We report differential effects of various compounds on inhibition of histamine release from washed leukocytes stimulated through IgE (using antigen or anti-IgE antibody) or N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) receptors. Inhibition of IgE-induced release was seen for several compounds listed in order of potency (IC50 in microM): CI-922 (3,7-dimethoxy-4-phenyl-N-(1-H-tetrazol-5-yl)-4-H-furo-[3, 2-b]-indole-2-carboxamide, 1-arginate) less than NDGA less than BW755c less than proxicromil less than isamoxole less than phenidone. Other compounds including FPL 55712, meclofenamate, and indomethacin were inactive or enhanced IgE-mediated release. When FMLP was used to stimulate histamine release the order of potency (IC50) changed: meclofenamate = FPL 55712 = proxicromil less than CI-922 less than NDGA = BW755c less than indomethacin less than isamoxole = phenidone. The inhibition of FMLP-induced histamine release by FPL 55712, meclofenamate and indomethacin in the absence of inhibition (or even enhancement) of histamine release by the IgE mechanism suggests that different pathways of activation and/or control are critical in the release process when different stimuli are used to activate basophils.