title: Toll-like receptor-4 is involved in eliciting an LPS-induced oxidative burst in neutrophils.
abstract: The lipopolysaccharide (LPS) receptor complex of mononuclear phagocytes is composed of Toll-like receptor-4 (TLR4), MD-2 and CD14. Other phagocyte populations may express similar LPS receptors. The transmembrane glycoprotein TLR4 was shown to induce or upregulate a variety of gene products, which collectively are the mediators of an LPS effect. In this study, an involvement of TLR4 in mediation of an oxidative burst was determined using murine peritoneal exsudate neutrophils and lucigenin-enhanced chemiluminescence (CL). The CL response was dependent on the LPS dose and the presence of serum, putatively a source of lipopolysaccharide-binding protein (LBP). In the absence of serum, a CL signal was elicited by 4 microg/ml LPS in peritoneal exsudate cells (PEC) from TLR4-sufficient (C3H/HeN) but not TLR4 deficient (C3H/HeJ) mice. The signal obtained in PEC from TLR4-sufficient mice was completely abrogated by superoxide dismutase (SOD), which indicated that the response depended on the formation of superoxide anion, and was also seen in purified neutrophils but not purified macrophages (Mphi). In the presence of serum, lower LPS concentrations (e.g. 40 ng/ml) elicited a strong CL response in PEC from TLR4-sufficient, and a weak signal in cells from TLR-4-deficient mice. This suggests that TLR4 engagement is involved in promoting an oxidative burst in murine neutrophils.
authors.affiliation: Institute of Veterinary Virology, University of Berne, Laenggass-Strasse 122, CH-3012, Berne, Switzerland.
authors.forename: Katharina A
authors.initials: KA
authors.lastname: Remer
authors.forename: Marija
authors.initials: M
authors.lastname: Brcic
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Jungi
mesh_terms: D000209:Acute-Phase Proteins; D000818:Animals; D002352:Carrier Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016897:Respiratory Burst / Q000502:physiology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000099231:Lipopolysaccharide-Binding Protein