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Infection and Immunity, December 2003, p. 6747-6753, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6747-6753.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Lipopolysaccharide Binding Protein Is an Essential Component of the Innate Immune Response to Escherichia coli Peritonitis in Mice

Sylvia Knapp,1* Alex F. de Vos,1 Sandrine Florquin,2 Douglas T. Golenbock,3 and Tom van der Poll1,4

Laboratory of Experimental Internal Medicine,1 Departments of Pathology,2 Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands,4 Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 016053

Received 12 July 2003/ Returned for modification 2 September 2003/ Accepted 8 September 2003

Lipopolysaccharide (LPS) binding protein (LBP) is an acute-phase protein that enhances the responsiveness of immune cells to LPS by virtue of its capacity to transfer LPS to CD14. To determine the role of LBP in the innate immune response to peritonitis, LBP gene-deficient (LBP-/-) and normal wild-type mice were intraperitoneally infected with Escherichia coli, the most common causative pathogen of this disease. LBP was detected at low concentrations in peritoneal fluid of healthy wild-type mice, and the local LBP levels increased rapidly upon induction of peritonitis. LBP-/- mice were highly susceptible to E. coli peritonitis, as indicated by accelerated mortality, earlier bacterial dissemination to the blood, impaired bacterial clearance in the peritoneal cavity, and more severe remote organ damage. LBP-/- mice displayed diminished early tumor necrosis factor alpha, interleukin-6, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein 2 production and attenuated recruitment of polymorphonuclear leukocytes to the site of infection, indicating that acute inflammation was promoted by LBP. Locally produced LBP is an essential component of an effective innate immune response to E. coli peritonitis.


* Corresponding author. Mailing address: Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, G2-132, 1105 AZ Amsterdam, The Netherlands. Phone: 31-20-566 5910. Fax: 31-20-697 7192. E-mail: s.knapp{at}amc.uva.nl.

Editor: B. B. Finlay


Infection and Immunity, December 2003, p. 6747-6753, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6747-6753.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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