Differential activation of human basophils by anti-IgE and formyl-methionyl-leucyl-phenylalanine. Indications for protein kinase C-dependent and -independent activation pathways.
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 greater than 240 s) was more than 20-fold slower than the almost instantaneous release upon stimulation with fMLP (t1/2 less than 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.
Knol
E F
EF
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Koenderman
L
L
Mul
F P
FP
Verhoeven
A J
AJ
Roos
D
D
D000470:Alkaloids / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000077191:Wortmannin
D000470:Alkaloids; D000730:Androstadienes; D000888:Antibodies, Anti-Idiotypic; D007073:Immunoglobulin E; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin