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.

Virulence and Immunomodulatory Roles of Bacterial Outer Membrane Vesicles

“…As a result, they concluded that vesicle-associated LPS is the native presentation of LPS that has the highest biological activity. In a similar comparison, endotoxin secreted into the culture supernatant from N. meningitidis cells was found to more effectively stimulate monocyte expression of plasminogen activator and the procoagulant factor TF than phenol-extracted, pure LPS (119).…”

“…Vesicles from Treponema denticola, a periodontopathogen, have active proteases that confer host cell-damaging characteristics similar to those of the whole bacterium (19,116,119). In addition, Neisseria meningitidis culture supernatant endotoxic filtrates have procoagulant and fibrinolytic factors for human monocytes (119).…”

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

“…Most of our knowledge of sepsis-induced DIC originates from infusion experiments with endotoxin, TNF, or other cytokines such as IL-1 and IL-6 and in vitro experiments with monocytes or endothelial cells exposed to these compounds (287,288,412,486). One of the initial procoagulant processes elicited was the expression of TF, the initial step in the activation of the extrinsic coagulation pathway (218) that ultimately results in thrombin formation.…”

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

“…Most of our knowledge of sepsis-induced DIC originates from infusion experiments with endotoxin, TNF, or other cytokines such as IL-1 and IL-6 and in vitro experiments with monocytes or endothelial cells exposed to these compounds (287,288,412,486). One of the initial procoagulant processes elicited was the expression of TF, the initial step in the activation of the extrinsic coagulation pathway (218) that ultimately results in thrombin formation.…”