Involvement of p38-mitogen-activated protein kinase in Staphylococcus aureus-induced neutrophil apoptosis.
Apoptosis occurred in human neutrophils within an hour of exposure to viable serum-opsonized Staphylococcus aureus, as indicated by appearance of cells with condensed nuclei, fragmented DNA, and increased phosphatidylserine exposure. In contrast, serum-opsonized, heat-killed S. aureus did not induce apoptosis. This discrepancy could not be explained by differences in bacterial uptake or total NADPH-oxidase activity. Suppressing phagocytosis by pretreating the neutrophils with cytochalasin b or by using nonopsonized bacteria did not prevent apoptosis. A supernatant from bacteria grown for 2 h in nutrient broth had a strong proapoptotic influence that was abrogated by heat treatment. Exposure to viable S. aureus or supernatant also led to activation of p38-mitogen-activated protein kinase in the neutrophils. Inhibition of this kinase with SB203580 reduced the apoptosis-inducing capacity of both bacteria and supernatant. We conclude that S. aureus activates p38-mitogen-activated protein kinase in neutrophils and induces apoptosis, probably mediated by a bacteria-derived soluble factor(s).
Lundqvist-Gustafsson
H
H
Division of Pathology II, Linköping University, Faculty of Health Sciences, Linköping, Sweden. helen.lundqvist@pat.liu.se
Norrman
S
S
Nilsson
J
J
Wilsson A
D017209:Apoptosis; D002467:Cell Nucleus / Q000648:ultrastructure; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D019255:NADPH Oxidases / Q000502:physiology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D010587:Phagocytosis; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D048051:p38 Mitogen-Activated Protein Kinases
D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580