Induction of human endothelial tissue factor expression byNeisseria 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 anin vitromodel of human endothelial TF expression, defined strains ofNeisseria meningitidiswere found to upregulate endothelial cell procoagulant activity (PCA) in a dose dependent manner. This TF response was detected with as little as 104cfu/ml and reached similar levels to those seen with high concentrations of purified endotoxin (>1 ng/ml). Treatment ofN. meningitidiswith 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 byN. meningitidis. Incubation of endothelial cells withN. meningitidisB1940 and B1940siaD- (an eight-fold more adherent unencapsulated isogenic strain), revealed a significantly greater TF response to B1940siaD- (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 toN. meningitidisand the consequent coagulopathy commonly associated with the disease.