Competition between bactericidal/permeability-increasing protein and lipopolysaccharide-binding protein for lipopolysaccharide binding to monocytes.
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 CD14 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 (TNF alpha) 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 TNF alpha 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.
Heumann
D
D
Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Gallay
P
P
Betz-Corradin
S
S
Barras
C
C
Baumgartner
J D
JD
Glauser
M P
MP
D000209:Acute-Phase Proteins; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001667:Binding, Competitive; D001798:Blood Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051379:Mice; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D016650:Fluorescein-5-isothiocyanate; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C021623:bactericidal permeability increasing protein