Effect of Staphylococcus aureus delta-toxin on human granulocyte functions and platelet-activating-factor metabolism.
The production of delta-toxin is supposed to be responsible for various pathophysiological effects during infection with Staphylococcus aureus. We compared the effects of delta-toxin with the structurally related bee venom toxin melittin on granulocyte functions and inflammatory mediator release. Delta-toxin and melittin induced a rapid Ca2+ influx, as was shown by fluorescence detection. Furthermore, oxygen radical production, as determined by luminol-enhanced chemiluminescence, was triggered by delta-toxin (0.15 to 15 micrograms/ml), whereas melittin showed only marginal effects. Release of lysozyme and beta-glucuronidase was observed only at high concentrations of 15 micrograms of melittin and delta-toxin per ml. Preincubation (15 min) of neutrophils with both toxins resulted in the formation of 3H-platelet-activating factor (3H-PAF) from 3H-lyso-PAF. After 5 min of incubation, the exogenously added lyso-PAF was converted to PAF (delta-toxin, 80 +/- 2%; melittin, 27 +/- 12% of total radioactivity; n = 3, mean +/- standard error of the mean) and 1-O-alkyl-2-acyl-glycerophosphorylcholine (alkyl-acyl-GPC) (corresponding values, 20 +/- 3% and 51 +/- 14% of total radioactivity). The newly generated PAF was rapidly metabolized to lyso-PAF and alkyl-acyl-GPC during the subsequent incubation period of 60 min. In the absence of any toxin, no formation of PAF from lyso-PAF was observed. Further studies indicated that the metabolism of PAF into lyso-PAF and alkyl-acyl-GPC was inhibited in the presence of delta-toxin. Melittin had no significant effects on PAF metabolism. Neither delta-toxin nor melittin modulated the uptake of PAF and lyso-PAF significantly. Our data provide evidence that delta-toxin has an effect on the activity of neutrophil granulocytes with regard to its proinflammatory capacity.
Kasimir
S
S
Medizinische Mikrobiologie und Immunologie, AG Infektabwehrmechanismen, Ruhr Universität, Bochum, Federal Republic of Germany.
Schönfeld
W
W
Alouf
J E
JE
König
W
W
D001427:Bacterial Toxins / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005609:Free Radicals; D005966:Glucuronidase / Q000378:metabolism; D006098:Granulocytes / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008555:Melitten / Q000494:pharmacology; D009113:Muramidase / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000472:pathogenicity*
D001427:Bacterial Toxins; D005609:Free Radicals; D010972:Platelet Activating Factor; C025971:staphylococcal delta toxin; D008555:Melitten; D009113:Muramidase; D005966:Glucuronidase; D010100:Oxygen; D002118:Calcium