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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
The Carboxyl-terminal Domain of Closely Related Endotoxin-binding
Proteins Determines the Target of Protein-Lipopolysaccharide
Complexes*
Nicole
Iovine ,
Joshua
Eastvold§,
Peter
Elsbach ,
Jerrold P.
Weiss§¶, and
Theresa Lee
Gioannini§ **
From the 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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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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