title: The role of tumour necrosis factor in the kinetics of lipopolysaccharide-mediated neutrophil priming in whole blood.
abstract: Neutrophils can be primed by bacterial lipopolysaccharide (LPS) for an enhanced oxidative burst, which is a key element in the pathogenesis of Gram-negative sepsis. Some serum proteins (e.g. lipopolysaccharide-binding protein) avidly bind LPS and markedly enhance receptor binding and cellular activation while other serum factors (lipoproteins, bactericidal/permeability-increasing protein) neutralize LPS and prevent neutrophil activation. In this paper we examined the kinetics of this priming reaction in whole blood. To study the balance between neutrophil activation and LPS neutralization a sensitive chemiluminescence assay was used in a whole blood system. LPS was able to prime neutrophils for enhanced oxidative burst in whole blood with an optimum incubation time of 25 min. However, LPS was neutralized very rapidly with a t(1/2) of 10 min. After 20 min a second priming factor was already generated, which was shown to be monocyte-derived tumour necrosis factor (TNF).
authors.affiliation: Department of Intensive Care and Clinical Toxicology, University Medical Center Utrecht, the Netherlands. hj.van.leeuwen@rivm.nl
authors.forename: H J
authors.initials: HJ
authors.lastname: van Leeuwen
authors.forename: M
authors.initials: M
authors.lastname: Van Der Tol
authors.forename: J A G
authors.initials: JA
authors.lastname: Van Strijp
authors.forename: J
authors.initials: J
authors.lastname: Verhoef
authors.forename: K P M
authors.initials: KP
authors.lastname: van Kessel
mesh_terms: D000900:Anti-Bacterial Agents / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008163:Luminescent Measurements / Q000379:methods; D009000:Monocytes / Q000276:immunology; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D011112:Polymyxin B / Q000276:immunology; D016897:Respiratory Burst / Q000276:immunology; D012486:Salmonella typhimurium; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D011112:Polymyxin B