Differential activation of human basophils by anti‐IgE and formyl‐methionyl‐leucylphenylalanine. Indications for protein kinase C‐dependent and ‐independent activation pathways

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Abstract
Upon activation, basophilic granulocytes release inflammatory mediators such as histamine. We studied histamine release of human basophils (64.1 ± 9.6% pure) after cross‐linking of membrane‐bound IgE via anti‐IgE, or after binding of the chemoattractant formyl‐methionyl‐leucyl‐phenylalanine (fMLP).A variability in the extent of histamine release upon stimulation by either anti‐IgE or fMLP was found between donors. Kinetic studies revealed that the histamine release induced by anti‐IgE (t1/2 > 240 s) was more than 20‐fold slower than the almost instantaneous release upon stimulation with fMLP (t1/2 < 10 s). Differences in the cell activation pathways triggered by these stimuli were further analyzed with staurosporine, an inhibitor of protein kinase C (PKC) and with wortmannin, an inhibitor of a PKC‐independent pathway. Inhibition of PKC resulted in a partial inhibition of the anti‐IgE‐induced release, whereas the fMLP‐induced release was slightly potentiated. The anti‐IgE‐induced release was completely inhibited in the presence of wortmannin. This inhibitor too, had no effect on the fMLP‐induced release. We conclude that major differences exist in the signal‐response coupling between the anti‐IgE and fMLP‐induced histamine release in human basophils. The so‐called releasability of human basophils may be due to the availability of different cell activation pathways.