Competition between Bactericidal/Permeability-Increasing Protein and Lipopolysaccharide-Binding Protein for Lipopolysaccharide Binding to Monocytes

Abstract

The bactericidal/permeability-increasing protein (BPI) inhibits the lipopolysaccharide (LPS)mediated activation of monocytes. Due to its inhibitory activity for various LPS, BPI has therapeutic potential in endotoxic shock. To be efficient in vivo, BPI should overcome the action of LPS-binding protein (LBP), a serum molecule that increases the expression of LPS-inducible genes via CD 14 of monocytes. rBPI₂₃, a recombinant fragment of BPI, prevented in a dose-dependent manner the binding and the internalization of LPS mediated by LBP. Consequently, rBPI₂₃ also inhibited LPS-induced tumor necrosis factor (TNFα) synthesis from monocytes. LPS- and LBP-mediated activation of monocytes was totally inhibited when LPS was preincubated with rBPI₂₃. Adding rBPI₂₃ at the same time as LBP resulted in an important but partial inhibition of TNFα release, but this inhibition vanished with delaying the time of addition of rBPI₂₃. These studies suggest that the inhibitory activity of BPI is related to its ability to compete with LBP for LPS.