PMID- 1652558 OWN - NLM STAT- MEDLINE DCOM- 19911002 LR - 20210526 IS - 0019-9567 (Print) IS - 1098-5522 (Electronic) IS - 0019-9567 (Linking) VI - 59 IP - 9 DP - 1991 Sep TI - Regulation of leukotriene B4 generation from human polymorphonuclear granulocytes after stimulation with formyl-methionyl-leucyl phenylalanine: effects of pertussis and cholera toxins. PG - 3046-52 AB - The effects of holotoxins and toxin subunits from Bordetella pertussis and Vibrio cholerae strains on intact and digitonin-permeabilized human polymorphonuclear neutrophils were studied. Our data clearly demonstrate that formyl-methionyl-leucyl-phenylalanine (fMLP)-induced generation of chemotactic active leukotriene B4 was inhibited by both holotoxins as well as by their isolated enzymatic A protomers. In contrast, the respective binding components (B oligomers) did not affect leukotriene formation. Priming of digitonin-permeabilized neutrophils with either guanylylimidodiphosphate or inositol trisphosphate increased subsequent stimulation with fMLP. In contrast, diacylglycerol decreased fMLP-induced leukotriene B4 formation, but inositol trisphosphate and diacylglycerol had no effect on inhibition mediated by the toxins. In addition, pertussis and cholera toxins reduced the specific binding of [3H]fMLP. Scatchard plot analysis revealed that the observed decrease of peptide binding was due to a reduced number of receptor sites. The fMLP-stimulated [3H]guanylylimidodiphosphate binding and GTPase activity used as parameters for the activation of G proteins were decreased in parallel. These results suggest altered chemotactic receptor numbers and G-protein functions responsible for the toxin-dependent suppression of fMLP-mediated response for neutrophils. FAU - Hensler, T AU - Hensler T AD - Lehrstuhl fur Medizinische Mikrobiologie und Immunologie, Ruhr-Universitat Bochum, Germany. FAU - Koller, M AU - Koller M FAU - Konig, W AU - Konig W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Phosphatidylinositols) RN - 0 (Receptors, Formyl Peptide) RN - 0 (Receptors, Immunologic) RN - 0 (Virulence Factors, Bordetella) RN - 1HGW4DR56D (Leukotriene B4) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - 9012-63-9 (Cholera Toxin) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Cholera Toxin/*pharmacology MH - GTP-Binding Proteins/immunology/metabolism MH - Humans MH - Leukotriene B4/*immunology MH - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology MH - Neutrophils/*immunology/metabolism MH - Permeability MH - Phosphatidylinositols/immunology/metabolism MH - Receptors, Formyl Peptide MH - Receptors, Immunologic/immunology MH - Signal Transduction MH - Virulence Factors, Bordetella/*pharmacology PMC - PMC258133 EDAT- 1991/09/01 00:00 MHDA- 1991/09/01 00:01 PMCR- 1991/09/01 CRDT- 1991/09/01 00:00 PHST- 1991/09/01 00:00 [pubmed] PHST- 1991/09/01 00:01 [medline] PHST- 1991/09/01 00:00 [entrez] PHST- 1991/09/01 00:00 [pmc-release] AID - 10.1128/iai.59.9.3046-3052.1991 [doi] PST - ppublish SO - Infect Immun. 1991 Sep;59(9):3046-52. doi: 10.1128/iai.59.9.3046-3052.1991.