Control of the oxidative burst of human neutrophils by staphylococcal leukotoxins.
The ability of staphylococcal two-component leukotoxins to induce an oxidative burst and/or to prime human polymorphonuclear cells (PMNs) was studied by using spectrofluorometry or flow cytometry. At sublytic concentrations, the HlgA-HlgB, HlgA-LukF-PV, LukS-PV-LukF-PV, and HlgC-LukF-PV combinations of leukotoxins, but not the LukS-PV-HlgB and HlgC-HlgB combinations, were able to induce H(2)O(2) production similar to the H(2)O(2) production induced by 1 micro M N-formyl-Met-Leu-Phe (fMLP). In addition, when added at sublytic concentrations, all of the leukotoxin combinations primed PMNs for H(2)O(2) production induced by fMLP. Leukotoxin activation was dependent on the presence of Ca(2+) and was inhibited by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, but not by N-methyl-L-arginine, an inhibitor of NO generation, which eliminates the possibility that NO plays a role in the action of leukotoxins. At higher concentrations, all leukotoxins inhibited H(2)O(2) production by PMNs activated by fMLP, phorbol 12-myristate 13-acetate (PMA), or the leukotoxins themselves. This inhibition was not related to the pore formation induced by leukotoxins. Intracellular release of H(2)O(2) induced by fMLP and PMA was not primed by leukotoxins but was inhibited. It seems that leukotoxin inhibition of H(2)O(2) release is independent of pore formation but secondary to an intracellular event, as yet unknown, triggered by leukotoxins.
Colin
Didier A
DA
Laboratoire de Physiopathologie et d'Antibiologie des Infections Bactériennes Emergentes et Nosocomiales, UPRES-EA 3432, Institut de Bactériologie, Université Louis Pasteur-Hôpitaux Universitaires de Strasbourg, France. didier.colin@medecine.u-strasbg.fr
Monteil
Henri
H
D002118:Calcium / Q000378:metabolism; D005098:Exotoxins / Q000633:toxicity*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects*; D013210:Staphylococcus / Q000472:pathogenicity*
D005098:Exotoxins; C018579:leukotoxin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D002118:Calcium