Cutting edge: cationic antimicrobial peptides block the binding of lipopolysaccharide (LPS) to LPS binding protein.
We investigated the mechanism by which cationic antimicrobial peptides block the activation of macrophages by LPS. The initial step in LPS signaling is the transfer of LPS to CD14 by LPS binding protein (LBP). Because many cationic antimicrobial peptides bind LPS, we asked whether these peptides block the binding of LPS to LBP. Using an assay that measures the binding of LPS to immobilized LBP, we show for the first time that a variety of structurally diverse cationic antimicrobial peptides block the interaction of LPS with LBP. The relative ability of different cationic peptides to block the binding of LPS to LBP correlated with their ability to block LPS-induced TNF-alpha production by the RAW 264.7 macrophage cell line.
Scott
M G
MG
Department of Microbiology, University of British Columbia, Vancouver, Canada.
Vreugdenhil
A C
AC
Buurman
W A
WA
Hancock
R E
RE
Gold
M R
MR
D000209:Acute-Phase Proteins; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D001667:Binding, Competitive / Q000276:immunology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002460:Cell Line; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008562:Membrane Glycoproteins; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000276:immunology; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010455:Peptides; D011506:Proteins; D000099231:Lipopolysaccharide-Binding Protein