ROLE OF THE LIPOPOLYSACCHARIDE (LPS)-BINDING PROTEIN CD14 PATHWAY IN LPS INDUCTION OF TISSUE FACTOR EXPRESSION IN MONOCYTIC CELLS

Endotoxic shock is associated with a coagulopathy, organ failure, and death. Tissue factor (TF) expression by monocytes exposed to bacterial endotoxin (lipopolysaccharide [LPS]) may mediate the coagulopathy and contribute to the high mortality of this disease. We examined the rol e of the LPS-binding protein (LBP)/CD14 receptor pathway in the LPS in duction of TF expression in human monocytic THP-1 cells and peripheral blood monocytes. In THP-1 cells, the threshold concentration of LPS r equired to induce TF activity in serum-free medium was reduced 20-fold by purified LBP, which also enhanced TF mRNA synthesis. Similarly, mo nocytes cultured in the presence of serum were induced to express TF a ntigen at LPS concentrations 100 times lower than monocytes cultured i n serum-free medium. An anti-LBP monoclonal antibody indicated that th is effect was dependent on the presence of LBP in serum. LPS/LBP induc tion of TF activity and TF antigen expression in these monocytic cells were also inhibited by an anti-CD14, monoclonal antibody, indicating a requirement for the CD14 receptor. Thus, we suggest that low levels of LPS (5 to 100 pg/mL) present during sepsis induce TF expression in monocytes via the LBP/CD14-dependent pathway.