LIPOPOLYSACCHARIDE (LPS) NEUTRALIZING PEPTIDES REVEAL A LIPID A BINDING-SITE OF LPS BINDING-PROTEIN

Endotoxic shock follows a cascade of events initiated by release of li popolysaccharide during infection with Gram-negative organisms. Two ov erlapping 15-mer peptides were identified, corresponding to residues 9 1-108 of human lipopolysaccharide binding protein that specifically bo und the lipid A moiety of lipopolysaccharide with high affinity. The p eptides inhibited binding of lipopolysaccharide to lipopolysaccharide binding protein, inhibited the chromogenic Limulus amebocyte lysate re action, and blocked release of tumor necrosis factor a following lipop olysaccharide challenge both in vitro and in vivo. These results sugge st lipopolysaccharide binding protein residues 91-108 form at least pa rt of the lipopolysaccharide binding site. Moreover, derivatives of li popolysaccharide binding protein residues 91-108 might modulate lipopo lysaccharide toxicity in the clinical setting.