This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by de Haas, C. J. C.
Right arrow Articles by van Strijp, J. A. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by de Haas, C. J. C.
Right arrow Articles by van Strijp, J. A. G.

 Previous Article  |  Next Article 

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.

Lipopolysaccharide (LPS)-Binding Synthetic Peptides Derived from Serum Amyloid P Component Neutralize LPS

Carla J. C. de Haas,1,* Ruurd van der Zee,2 Barry Benaissa-Trouw,1 Kok P. M. van Kessel,1 Jan Verhoef,1 and Jos A. G. van Strijp1

Department of Inflammation, Eijkman Winkler Institute,1 and Faculty of Veterinary Medicine, Institute of Infectious Diseases and Immunology,2 University Utrecht, Utrecht, The Netherlands

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.


* 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.



This article has been cited by other articles:

  • Berbee, J. F. P., van der Hoogt, C. C., Kleemann, R., Schippers, E. F., Kitchens, R. L., van Dissel, J. T., Bakker-Woudenberg, I. A. J. M., Havekes, L. M., Rensen, P. C. N. (2006). Apolipoprotein CI stimulates the response to lipopolysaccharide and reduces mortality in Gram-negative sepsis. FASEB J. 20: 2162-2164 [Abstract] [Full Text]  
  • Noursadeghi, M., Bickerstaff, M. C. M., Gallimore, J. R., Herbert, J., Cohen, J., Pepys, M. B. (2000). Role of serum amyloid P component in bacterial infection: Protection of the host or protection of the pathogen. Proc. Natl. Acad. Sci. USA 97: 14584-14589 [Abstract] [Full Text]  
  • Scott, M. G., Rosenberger, C. M., Gold, M. R., Finlay, B. B., Hancock, R. E. W. (2000). An {alpha}-Helical Cationic Antimicrobial Peptide Selectively Modulates Macrophage Responses to Lipopolysaccharide and Directly Alters Macrophage Gene Expression. J. Immunol. 165: 3358-3365 [Abstract] [Full Text]