Leukotriene B4 generation and DNA fragmentation induced by leukocidin from Staphylococcus aureus: protective role of granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF for human neutrophils.
We studied the effect of leukocidin from Staphylococcus aureus V8 strains (Luk-PV) on the generation of Leukotriene B4 (LTB4) and its metabolites from human polymorphonuclear neutrophils (PMNs). Significant amounts of LTB4 were generated by PMNs after leukocidin exposure in a time- and dose-dependent manner, as shown by reversed-phase high-performance liquid chromatography analysis. In this regard, the S and F components of leukocidin acted synergistically. The calcium ionophore A23187 induced LTB4 generation, and the metabolism of exogenously added LTB4 into biologically less active omega-oxidated compounds was significantly decreased after leukocidin exposure. Priming of PMNs with granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF prior to leukocidin exposure substantially increased toxin- and calcium ionophore A23187-induced LTB4 formation. The inhibitory effects of leukocidin on mediator release were accompanied by membrane damage and DNA fragmentation, which were both restored after pretreatment with GM-CSF. The data suggest that the presence of costimulatory priming factors such as GM-CSF or G-CSF in the microenvironment of an inflammatory focus determines the pathophysiological effects induced by S. aureus leukocidin.
Hensler
T
T
Medizinische Mikrobiologie und Immunologie, Arbeitsgruppe Infektabwehr, Ruhr-Universität Bochum, Germany.
König
B
B
Prévost
G
G
Piémont
Y
Y
Köller
M
M
König
W
W
D000001:Calcimycin / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007956:Leukocidins / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D013211:Staphylococcus aureus / Q000472:pathogenicity*
D007956:Leukocidins; D016179:Granulocyte Colony-Stimulating Factor; D007975:Leukotriene B4; D000001:Calcimycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D007770:L-Lactate Dehydrogenase