Lipopolysaccharide (LPS)-binding synthetic peptides derived from serum amyloid P component neutralize LPS.
Lipopolysaccharide (LPS) is the major mediator of gram-negative septic shock. Molecules that bind LPS and neutralize its toxic effects could have important 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 study, we used a pepscan of overlapping 15-mer peptides and distinguished two additional LPS-binding regions within the SAP molecule, identified in the regions spanning amino acids 61 to 75 and 186 to 200. The corresponding SAP-derived peptides, pep61-75 and pep186-200, inhibited the binding of fluorescein isothiocyanate-labeled LPS to monocytes as efficiently as a bactericidal/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 with LPS to induce septic shock, indicating a potential use of this peptide in the defense against serious gram-negative sepsis in humans.
de Haas
C J
CJ
Department of Inflammation, Eijkman Winkler Institute, University Utrecht, The Netherlands. c.j.c.dehaas@lab.azu.nl
van der Zee
R
R
Benaissa-Trouw
B
B
van Kessel
K P
KP
Verhoef
J
J
van Strijp
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D009500:Neutralization Tests; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D016897:Respiratory Burst; D000683:Serum Amyloid P-Component / Q000138:chemical synthesis / Q000276:immunology*; D012772:Shock, Septic / Q000517:prevention & control
D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D010455:Peptides; D000683:Serum Amyloid P-Component; D006493:Heparin; D016650:Fluorescein-5-isothiocyanate