title: Induction of human endothelial tissue factor expression by Neisseria meningitidis: the influence of bacterial killing and adherence to the endothelium.
abstract: Tissue factor (TF), a small membrane bound high affinity receptor for factor VII, has an important procoagulant role in the haemostatic dysfunction associated with severe sepsis. Using an in vitro model of human endothelial TF expression, defined strains of Neisseria meningitidis were found to upregulate endothelial cell procoagulant activity (PCA) in a dose dependent manner. This TF response was detected with as little as 10(4) cfu/ml and reached similar levels to those seen with high concentrations of purified endotoxin (> 1 ng/ml). Treatment of N. meningitidis with either adult donor immune serum, penicillin or gentamicin failed to enhance this PCA. Limulus amoebocyte lysate assay of lipopolysaccharide in bacterial culture filtrates together with polymyxin B inhibition experiments suggest that endotoxin is largely responsible for endothelial TF induction by N. meningitidis. Incubation of endothelial cells with N. meningitidis B1940 and B1940 siaD- (an eight-fold more adherent unencapsulated isogenic strain), revealed a significantly greater TF response to B1940 siaD- (P < 0.01). In conclusion, bacterial adhesion to the vessel wall and therefore local levels of endotoxin may be important determinants of the endothelial procoagulant response to N. meningitidis and the consequent coagulopathy commonly associated with the disease.
authors.affiliation: Paediatric Infectious Diseases Unit, Imperial College School of Medicine at St Mary's, London, U.K.
authors.forename: R S
authors.initials: RS
authors.lastname: Heyderman
authors.forename: N J
authors.initials: NJ
authors.lastname: Klein
authors.forename: O A
authors.initials: OA
authors.lastname: Daramola
authors.forename: S
authors.initials: S
authors.lastname: Hammerschmidt
authors.forename: M
authors.initials: M
authors.lastname: Frosch
authors.forename: B D
authors.initials: BD
authors.lastname: Robertson
authors.forename: M
authors.initials: M
authors.lastname: Levin
authors.forename: C A
authors.initials: CA
authors.lastname: Ison
mesh_terms: D000328:Adult; D001422:Bacterial Adhesion; D016667:Bacterial Capsules; D001777:Blood Coagulation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000382:microbiology*; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D009345:Neisseria meningitidis / Q000502:physiology*; D011135:Polysaccharides, Bacterial / Q000494:pharmacology; D013925:Thromboplastin / Q000096:biosynthesis*; D014471:Umbilical Veins
chemical_list: D004731:Endotoxins; D011135:Polysaccharides, Bacterial; C039455:capsular polysaccharide, meningococcal group B; C044101:endotoxin, Escherichia coli; D013925:Thromboplastin