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Infection and Immunity, June 1999, p. 2790-2796, Vol. 67, No. 6
Department of Inflammation,
Received 23 October 1998/Returned for modification 29 January
1999/Accepted 23 March 1999
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.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Lipopolysaccharide (LPS)-Binding Synthetic Peptides
Derived from Serum Amyloid P Component Neutralize LPS
*
Corresponding author. Mailing address: Eijkman Winkler
Institute, Department of Inflammation, AZU, G04.614, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Phone: (31) 30-2507627. Fax:
(31) 30-2541770. E-mail:
c.j.c.dehaas{at}lab.azu.nl.
Infection and Immunity, June 1999, p. 2790-2796, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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