Lipopolysaccharide (LPS)-binding synthetic peptides derived from serum amyloid P component neutralize LPS

Lipopolysaccharide (LPS) is the major mediator of gram-negative septic shoc k Molecules that bind LPS and neutralize its toxic effects could have impor tant clinical applications. We showed that serum amyloid P component (SAP) neutralizes LPS. A SAP-derived peptide, consisting of amino acids 27 to 39, inhibited LPS-mediated effects in the presence of human blood. In this stu dy, we used a pepscan of overlapping 15-mer peptides and distinguished two additional LPS-binding regions within the SAP molecule, identified in the r egions spanning amino acids 61 to 75 and 186 to 200. The corresponding SAP- derived peptides, pep61-75 and pep186-200, inhibited the binding of fluores cein isothiocyanate-labeled LPS to monocytes as efficiently as a bactericid al/permeability-increasing protein (BPI)-derived 15-mer peptide comprising amino acids 85 to 99. The same SAP-derived peptides very potently inhibited LPS-induced priming of phagocytes in human blood. Also, SAP-derived pep186 -200 caused a prolonged survival of actinomycin D-sensitized mice treated w ith LPS to induce septic shock, indicating a potential use of this peptide in the defense against serious gram-negative sepsis in humans.