PMID- 1708341 OWN - NLM STAT- MEDLINE DCOM- 19910530 LR - 20181130 IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 21 IP - 4 DP - 1991 Apr TI - Differential activation of human basophils by anti-IgE and formyl-methionyl-leucyl-phenylalanine. Indications for protein kinase C-dependent and -independent activation pathways. PG - 881-5 AB - 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. FAU - Knol, E F AU - Knol EF AD - Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam. FAU - Koenderman, L AU - Koenderman L FAU - Mul, F P AU - Mul FP FAU - Verhoeven, A J AU - Verhoeven AJ FAU - Roos, D AU - Roos D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Alkaloids) RN - 0 (Androstadienes) RN - 0 (Antibodies, Anti-Idiotypic) RN - 37341-29-0 (Immunoglobulin E) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - EC 2.7.11.13 (Protein Kinase C) RN - H88EPA0A3N (Staurosporine) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - XVA4O219QW (Wortmannin) SB - IM MH - Alkaloids/pharmacology MH - Androstadienes/pharmacology MH - Antibodies, Anti-Idiotypic/*immunology MH - Basophils/drug effects/*metabolism MH - Cells, Cultured MH - *Histamine Release/drug effects MH - Humans MH - Immunoglobulin E/*immunology MH - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology MH - Protein Kinase C/*physiology MH - Staurosporine MH - Tetradecanoylphorbol Acetate/pharmacology MH - Wortmannin EDAT- 1991/04/01 00:00 MHDA- 1991/04/01 00:01 CRDT- 1991/04/01 00:00 PHST- 1991/04/01 00:00 [pubmed] PHST- 1991/04/01 00:01 [medline] PHST- 1991/04/01 00:00 [entrez] AID - 10.1002/eji.1830210404 [doi] PST - ppublish SO - Eur J Immunol. 1991 Apr;21(4):881-5. doi: 10.1002/eji.1830210404.