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Originally published In Press as doi:10.1074/jbc.M109622200 on December 31, 2001

J. Biol. Chem., Vol. 277, Issue 10, 7970-7978, March 8, 2002
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The Carboxyl-terminal Domain of Closely Related Endotoxin-binding Proteins Determines the Target of Protein-Lipopolysaccharide Complexes*

Nicole IovineDagger , Joshua Eastvold§, Peter ElsbachDagger , Jerrold P. Weiss§, and Theresa Lee Gioannini§||**

From the Dagger  Department of Medicine, New York University School of Medicine, New York, New York 10016, the Departments of || Biochemistry,  Microbiology, and § Internal Medicine, Division of Infectious Diseases, Inflammation Program, University of Iowa, and Veterans Affairs Medical Center, Iowa City, Iowa 52242

The bactericidal/permeability increasing (BPI) and lipopolysaccharide (LPS)-binding (LBP) proteins are closely related two-domain proteins in which LPS binding is mediated by the NH2-terminal domain. To further define the role of the COOH-terminal domain of these proteins in delivery of LPS to specific host acceptors, we have compared interactions of LBP, BPI, LBPN-BPIC (NH2-terminal domain of LBP, COOH-terminal domain of BPI), and BPIN-LBPC with purified 3H-LPS and, subsequently, with purified leukocytes and soluble (s)CD14. The COOH-terminal domain of LBP promotes delivery of LPS to CD14 on both polymorphonuclear leukocytes and monocytes resulting in cell activation. In the presence of Ca2+ and Mg2+, LBP and BPI each promote aggregation of LPS to protein-LPS aggregates of increased size (apparent Mr > 20 × 106 Da), but only LPS associated with LBP and BPIN-LBPC is disaggregated in the presence of CD14. BPI and LBPN-BPIC promote apparently CD14-independent LPS association to monocytes without cell activation. These findings demonstrate that the carboxyl-terminal domain of these closely related endotoxin-binding proteins dictates the route and host responses to complexes they form with endotoxin.


* This work was supported by United States Public Health Service Grants DK05472 and PO144642 (to J. W.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

** To whom correspondence should be addressed: University of Iowa, Dept. of Internal Medicine, GH 34W, Iowa City, IA 52242. Tel.: 319-338-0581 (ext. 7534); Fax: 319-339-7162, E-mail: theresa-gioannini@uiowa.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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