title: Inhibition by lipid A-specific monoclonal antibodies of priming of human polymorphonuclear leucocytes by endotoxin.
abstract: Exposure to lipopolysaccharide (LPS) primes polymorphonuclear leucocytes (PMNL) for enhanced release of oxygen metabolites after subsequent stimulation. The metabolic response of human PMNL primed with LPS and stimulated with formyl-methionyl-leucyl-phenylalanine (FMLP) was measured by chemiluminescence (CL) as a parameter for endotoxic activity. Polymyxin B (PMB) and monoclonal antibodies (MAbs) with specificity for lipid A were tested for inhibition of the priming effect of Re LPS of Salmonella minnesota R595, Rc LPS of Escherichia coli J5 and smooth LPS of E. coli O111. The CL response of PMNL primed with Re LPS or Rc LPS was higher than that of PMNL primed with smooth LPS. Pre-incubation of rough or smooth LPS with PMB caused dose-dependent inhibition of priming of PMNL. Two IgM MAbs, 8-2 and 26-20, which recognise different epitopes on the hydrophobic part of lipid A, also completely prevented priming of PMNL by either rough or smooth LPS. The dose-dependent inhibitory effect of both MAbs was similar to the inhibition by PMB. These results indicate that the binding of MAbs to the hydrophobic part of lipid A is important in blocking lipid A-mediated effects.
authors.affiliation: Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Cornelissen
authors.forename: C P
authors.initials: CP
authors.lastname: Van Kessel
authors.forename: E
authors.initials: E
authors.lastname: Brouwer
authors.forename: C A
authors.initials: CA
authors.lastname: Kraaijeveld
authors.forename: J
authors.initials: J
authors.lastname: Verhoef
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008050:Lipid A / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D012475:Salmonella
chemical_list: D000911:Antibodies, Monoclonal; D004731:Endotoxins; D008050:Lipid A; D008070:Lipopolysaccharides; D009240:N-Formylmethionine Leucyl-Phenylalanine