COMPETITION BETWEEN BACTERICIDAL PERMEABILITY-INCREASING PROTEIN AND LIPOPOLYSACCHARIDE-BINDING PROTEIN FOR LIPOPOLYSACCHARIDE BINDING TO MONOCYTES

The bactericidal/permeability-increasing protein (BPI) inhibits the li popolysaccharide (LPS)-mediated activation of monocytes. Due to its in hibitory activity for various LPS, BPI has therapeutic potential in en dotoxic shock. To be efficient in vivo, BPI should overcome the action of LPS-binding protein (LBP), a serum molecule that increases the exp ression of LPS-inducible genes via CD14 of monocytes. rBPI23, a recomb inant fragment of BPI, prevented in a dose-dependent manner the bindin g and the internalization of LPS mediated by LBP. Consequently, rBPI23 also inhibited LPS-induced tumor necrosis factor (TNFalpha) synthesis from monocytes. LPS- and LBP-mediated activation of monocytes was tot ally inhibited when LPS was preincubated with rBPI23. Adding rBPI23 at the same time as LBP resulted in an important but partial inhibition of TNFalpha release, but this inhibition vanished with delaying the ti me of addition of rBPI23. These studies suggest that the inhibitory ac tivity of BPI is related to its ability to compete with LBP for LPS.