1. GTP-binding proteins are involved in the modulated activity of human neutrophils treated with the Panton-Valentine leukocidin from Staphylococcus aureus.
- Author
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Hensler T, Köller M, Prévost G, Piémont Y, and König W
- Subjects
- Arachidonate 5-Lipoxygenase metabolism, Bacterial Toxins, Calcimycin pharmacology, Chemotaxis, Leukocyte physiology, Cholera Toxin pharmacology, Exotoxins, Guanylyl Imidodiphosphate metabolism, Humans, Neutrophils drug effects, Pertussis Toxin, Poly(ADP-ribose) Polymerases pharmacology, Receptors, Cell Surface metabolism, Receptors, Formyl Peptide, Receptors, Immunologic analysis, Receptors, Leukotriene B4 analysis, Receptors, Peptide analysis, Signal Transduction, Virulence Factors, Bordetella pharmacology, ras Proteins biosynthesis, GTP-Binding Proteins metabolism, Leukocidins pharmacology, Leukotriene B4 biosynthesis, Neutrophils metabolism, Staphylococcus aureus
- Abstract
Significant amounts of leukotriene B4 (LTB4) are generated by human polymorphonuclear neutrophils (PMNs) after incubation with the Panton-Valentine leukocidin (Luk-PV) from Staphylococcus aureus V8 strains. We showed that GTP-binding proteins (G proteins) are involved in the Luk-PV-activated signal transduction of PMNs. ADP-ribosylation of heterotrimeric G proteins by cholera and pertussis toxins decreased the Luk-PV-induced LTB4-generation. In contrast, ADP-ribosylation of the low-molecular-weight G proteins rho and rac by Clostridium botulinum exoenzyme C3 increased the Luk-PV-induced LTB4 synthesis. The subsequent stimulation of Luk-PV-treated PMNs by either calcium ionophore A23187, sodium fluoride, or formylmethionyl-leucyl-phenylalanine was significantly inhibited. This decrease was paralleled by a loss of G-protein functions, including GTPase activity and GTP-binding capacity. An increase of G-protein functions was obtained with low amounts of Luk-PV. In addition to the modulated G-protein functions, ADP-ribosylation of 24-, 40-, and 45-kDa proteins by Luk-PV was detected. As shown in control experiments, the ADP-ribosylated 24-kDa proteins were not substrates for C. botulinum exoenzyme C3. Introduction of ras p21 into digitonin-permeabilized PMNs was without effect on subsequent Luk-PV stimulation. In addition, the translocation of ras p21, ras GAP, and 5-lipoxygenase into the membrane of Luk-PV-treated PMNs, as well as the expression of chemotactic membrane receptors for LTB4 and formylmethionyl leucyl phenylalanine, was significantly diminished.
- Published
- 1994
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