Cationic antimicrobial peptides block the binding of lipopolysaccharide (LPS) to LPS binding protein

We investigated the mechanism by which cationic antimicrobial peptides bloc k the activation of macrophages by LPS. The initial step in LPS signaling i s the transfer of LPS to CD14 by LPS binding protein (LBP), Because many ca tionic antimicrobial peptides bind LPS, me asked whether these peptides blo ck the binding of LPS to LBP. Using an assay that measures the binding of L PS to immobilized LBP, we show for the first time that a variety of structu rally 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 TN F-alpha production by the RAW 264.7 macrophage cell line.