Lipopolysaccharide (LPS) Signal Transduction and Clearance
DUAL ROLES FOR LPS BINDING PROTEIN AND MEMBRANE CD14 (*)
- ↵§ To whom correspondence should be addressed: Dept. of Immunology, The Scripps Research Institute, 10666 North Torrey Pines Rd., La Jolla, CA 92037. Tel.: 619-554-8215; Fax: 619-554-3289.
Abstract
Under physiological conditions, lipopolysaccharide (LPS) activation of cells involves the LPS binding protein (LBP) and either membrane or soluble CD14. We find LPS forms a ternary complex with LBP and membrane CD14 (mCD14). Subsequent to complex formation and distinct from signal transduction, LBP and LPS internalize. Internalization can be separated from signal transduction with the anti-LBP antibody 18G4 and the anti-CD14 antibody 18E12. 18G4 inhibits LBP binding to mCD14 without blocking signal transduction or LPS transfer to soluble CD14; 18E12 inhibits signal transduction without affecting LPS binding and uptake. These data show that while LPS signal transduction and LPS clearance utilize both LBP and mCD14, the pathways bifurcate after LPS binding to mCD14.
Footnotes
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↵* This work was supported by National Institutes of Health Grants AI32021 (to P. S. T.) and AI15136 and GM28985 (to R. J. U.) and National Research Service Award Trainee Grant GM08172 and an American Heart Association Fellowship (to J. A. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Received October 24, 1994.
- Revision received January 4, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
