Previous Article | Next Article ![]()
Infection and Immunity, November 2001, p. 6942-6950, Vol. 69, No. 11
Department of Immunochemistry and Biochemical
Microbiology, Center for Medicine and Biosciences, Research Center
Borstel, D-23845 Borstel, Germany1; XOMA
(US) LLC, Berkeley, California 947102; and
Institute for Biological Sciences, National Research Council of
Canada, Ottawa, Ontario, Canada K1A OR63
Received 26 April 2001/Returned for modification 2 August
2001/Accepted 20 August 2001
The lipopolysaccharide (LPS)-binding protein (LBP) has a
concentration-dependent dual role in the pathogenesis of gram-negative sepsis: low concentrations of LBP enhance the LPS-induced activation of
mononuclear cells (MNC), whereas the acute-phase rise in LBP concentrations inhibits LPS-induced cellular stimulation. In
stimulation experiments, we have found that LBP mediates the
LPS-induced cytokine release from MNC even under serum-free conditions.
In biophysical experiments we demonstrated that LBP binds and
intercalates into lipid membranes, amplified by negative charges of the
latter, and that intercalated LBP can mediate the CD14-independent
intercalation of LPS into membranes in a lipid-specific and
temperature-dependent manner. In contrast, prior complexation of LBP
and LPS inhibited binding of these complexes to membranes due to
different binding of LBP to LPS or phospholipids. This results in a
neutralization of LPS and, therefore, to a reduced production of tumor
necrosis factor by MNC. We propose that LBP is not only present as a
soluble protein in the serum but may also be incorporated as a
transmembrane protein in the cytoplasmic membrane of MNC and that the
interaction of LPS with membrane-associated LBP may be an important
step in LBP-mediated activation of MNC, whereas LBP-LPS complexation in the serum leads to a neutralization of LPS.
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.11.6942-6950.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Dual Role of Lipopolysaccharide (LPS)-Binding Protein
in Neutralization of LPS and Enhancement of LPS-Induced
Activation of Mononuclear Cells
*
Corresponding author. Mailing address: Research Center
Borstel, Center for Medicine and Biosciences, Department of
Immunochemistry and Biochemical Microbiology, Parkallee 10, D-23845
Borstel, Germany. Phone: 49 (0) 4537 188-232. Fax: 49 (0) 4537 188-632. E-mail: useydel{at}fz-borstel.de.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|