INDUCTION OF HUMAN ENDOTHELIAL TISSUE FACTOR EXPRESSION BY NEISSERIA-MENINGITIDIS - THE INFLUENCE OF BACTERIAL KILLING AND ADHERENCE TO THEENDOTHELIUM

Tissue factor (TF), a small membrane bound high affinity receptor for factor VII, has an important procoagulant role in the haemostatic dysf unction associated with severe sepsis. Using an in vitro model of huma n 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 lit tle as 10(4) cfu/ml and reached similar levels to those seen with high concentrations of purified endotoxin (> 1 ng/ml). Treatment of N. men ingitidis with either adult donor immune serum, penicillin or gentamic in failed to enhance this PCA. Limulus amoebocyte lysate assay of lipo polysaccharide 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 endoth elial cells with N. meningitidis B1940 and B1940 siaD- (an eight-fold more adherent unencapsulated isogenic strain), revealed a significantl y greater TF response to B1940 siaD- (P<0.01). In conclusion, bacteria l 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 associate d with the disease. (C) 1997 Academic Press Limited.