title: Endotoxin liberation from Neisseria meningitidis correlates to their ability to induce procoagulant and fibrinolytic factors in human monocytes.
abstract: Endotoxin released from different strains of Neisseria meningitidis were studied for their ability to induce procoagulant (tissue factor, TF), fibrinolytic (plasminogen activator, PA) and antifibrinolytic (plasminogen activator inhibitor 2, PAI-2) factors in human monocytes. Two meningococcal strains that liberate endotoxin (E+; 270+ and 840+) and 2 non-liberating (E-; 270- and 840-) strains were used. The endotoxin activity in culture filtrates of these strains was monitored with the Limulus amoebocyte lysate (LAL) test. There was a marked difference between E+ and E- strains in their ability to liberate endotoxin. Suspensions of whole bacteria of all 4 strains induced a significant (14-19-fold) increase in monocyte TF expression when present in concentrations > 10(5) CFU/ml. At lower concentrations (10(4) CFU/ml), E+ strains were clearly more potent stimulators of TF synthesis than E- strains. Culture filtrates of E+ strains were up to 10(4)-fold more potent in inducing TF synthesis than filtrates from E- strains. This marked difference in inducing potency between E+ and E- strains was also observed when monocyte PAI-2 synthesis was examined. The PA expression, on the other hand, was suppressed when monocytes were incubated in the presence of culture filtrates, especially filtrates from the E+ strains. The increased procoagulant and antifibrinolytic activity, together with reduced profibrinolytic activity of monocytes, was closely correlated to the amount of endotoxin measured in the culture filtrates. These changes may contribute substantially to the coagulopathic state seen during systemic meningococcal disease.
authors.affiliation: Department of Surgery, Ullevaal University Hospital, Oslo, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Schlichting
authors.forename: T
authors.initials: T
authors.lastname: Lyberg
authors.forename: O
authors.initials: O
authors.lastname: Solberg
authors.forename: B M
authors.initials: BM
authors.lastname: Andersen
mesh_terms: D002478:Cells, Cultured; D004731:Endotoxins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009345:Neisseria meningitidis; D017396:Plasminogen Activator Inhibitor 2 / Q000096:biosynthesis*; D010960:Plasminogen Activators / Q000096:biosynthesis* / Q000187:drug effects; D013925:Thromboplastin / Q000096:biosynthesis* / Q000187:drug effects
chemical_list: D004731:Endotoxins; D017396:Plasminogen Activator Inhibitor 2; D013925:Thromboplastin; D010960:Plasminogen Activators