ENDOTOXIN LIBERATION FROM NEISSERIA-MENINGITIDIS CORRELATES TO THEIR ABILITY TO INDUCE PROCOAGULANT AND FIBRINOLYTIC FACTORS IN HUMAN MONOCYTES

Endotoxin released from different strains of Neisseria meningitidis we re studied for their ability to induce procoagulant (tissue factor, TF ), fibrinolytic (plasminogen activator, PA) and antifibrinolytic (plas minogen activator inhibitor 2, PAI-2) factors in human monocytes. Two meningococcal strains that liberate endotoxin (Ef; 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 be tween E+ and E- strains in their ability to liberate endotoxin. Suspen sions of whole bacteria of all 4 strains induced a significant (14-19- fold) increase in monocyte TF expression when present in concentration s >10(5) CFU/ml. At lower concentrations (10(4) CFU/ml), E+ strains we re clearly more potent stimulators of TF synthesis than E- strains. Cu lture filtrates of ES strains were up to 10(4)-fold more potent in ind ucing TF synthesis than filtrates from E- strains. This marked differe nce in inducing potency between E+ and E- strains was also observed wh en monocyte PAI-2 synthesis was examined. The PA expression, on the ot her hand, was suppressed when monocytes were incubated in the presence of culture filtrates, especially filtrates from the E+ strains. The i ncreased procoagulant and antifibrinolytic activity, together with red uced profibrinolytic activity of monocytes, was closely correlated to the amount of endotoxin measured in the culture filtrates. These chang es may contribute substantially to the coagulopathic state seen during systemic meningococcal disease.