GTP-binding proteins are involved in the modulated activity of human neutrophils treated with the Panton-Valentine leukocidin from Staphylococcus aureus.
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.
Medizinische Mikrobiologie und Immunologie, Ruhr-Universität Bochum, Germany.
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T
Hensler
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M
Köller
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G
Prévost
Y
Y
Piémont
W
W
König
D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001427:Bacterial Toxins; D000001:Calcimycin / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D002772:Cholera Toxin / Q000494:pharmacology; D005098:Exotoxins; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D006801:Humans; D007956:Leukocidins / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D011065:Poly(ADP-ribose) Polymerases / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000032:analysis; D018102:Receptors, Leukotriene B4 / Q000032:analysis; D018000:Receptors, Peptide / Q000032:analysis; D015398:Signal Transduction; D013211:Staphylococcus aureus; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D018631:ras Proteins / Q000096:biosynthesis
D001427:Bacterial Toxins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D018000:Receptors, Peptide; D010566:Virulence Factors, Bordetella; D007975:Leukotriene B4; D006165:Guanylyl Imidodiphosphate; D000001:Calcimycin; D002772:Cholera Toxin; D001094:Arachidonate 5-Lipoxygenase; D011065:Poly(ADP-ribose) Polymerases; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D018631:ras Proteins