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Murine Bactericidal/Permeability-Increasing Protein Inhibits the Endotoxic Activity of Lipopolysaccharide and Gram-Negative Bacteria¹

Microbiological Institute-Clinical Microbiology, Immunology and Hygiene, University of Erlangen-Nuremberg, Erlangen, Germany

Recognition of LPS by TLR4 initiates inflammatory responses inducing potent antimicrobial immunity. However, uncontrolled inflammatory responses can be detrimental. To prevent the development of septic shock during an infection with Gram-negative bacteria, the immune system has developed mechanisms to neutralize LPS by specialized proteins. In this study, we report the recombinant expression and functional characterization of the mouse homolog of human bactericidal/permeability-increasing protein (BPI). Purified recombinant mouse BPI was able to neutralize LPS-mediated activation of macrophages and to block LPS-dependent maturation of dendritic cells. Recombinant mouse BPI neutralized the capacity of Gram-negative bacteria to activate immune cells, but did not influence the stimulatory properties of Gram-positive bacteria. Unlike human BPI, mouse BPI failed to kill or inhibit the growth of Pseudomonas aeruginosa. Together, these data demonstrate that murine BPI is a potent LPS-neutralizing protein that may limit innate immune responses during Gram-negative infections.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in parts by grants from the German Research Foundation (to M.S.) and the Interdisziplinäres Zentrum für Klinische Forschung Erlangen (to A.G.).

² Address correspondence and reprint requests to Dr. Markus Schnare, Microbiological Institute-Clinical Microbiology, Immunology, and Hygiene, University Hospital of Erlangen, Wasserturmstrasse 3/5, 91054 Erlangen, Germany. E-mail address: markus.schnare{at}uk-erlangen.de

³ Abbreviations used in this paper: BPI, bactericidal/permeability-increasing protein; LBP, LPS-binding protein; rmBPI, recombinant mouse BPI; DC, dendritic cell; MOI, multiplicity of infection; BMDC, bone marrow-derived DC; AOAH, acyloxyacyl hydrolase.