HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 50, 36250-36256, December 14, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/50/36250    most recent M705995200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Teghanemt, A. Articles by Weiss, J. P. Search for Related Content PubMed PubMed Citation Articles by Teghanemt, A. Articles by Weiss, J. P. Social Bookmarking                      What's this?

Transfer of Monomeric Endotoxin from MD-2 to CD14

CHARACTERIZATION AND FUNCTIONAL CONSEQUENCES^*

Athmane Teghanemt, Polonca Prohinar, Theresa L. Gioannini^¶, and Jerrold P. Weiss^||1

From the Department of Internal Medicine and the Inflammation Program, the ^||Department of Microbiology, and the Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242 and the ^¶Veterans Affairs Medical Center, Iowa City, Iowa 52246

Potent Toll-like receptor 4 (TLR4)-dependent cell activation by endotoxin depends on sequential transfer of monomers of endotoxin from an aggregated form to CD14 via the lipopolysaccharide-binding protein and then to MD-2. We now show that monomeric endotoxin can be transferred in reverse from MD-2 to CD14 but not to lipopolysaccharide-binding protein. Reverse transfer requires a 1000-fold molar excess of CD14 to endotoxin-MD-2. Transfer of endotoxin from MD-2 to extracellular soluble CD14 reduces activation of cells expressing TLR4 without MD-2. However, transfer of endotoxin from MD-2 to membrane CD14 (mCD14) makes cells expressing MD-2·TLR4 sensitive to activation by the endotoxin-MD-2 complex. An endotoxin-mutant (F126A) MD-2 complex that does not activate cells expressing TLR4 alone potently activates cells expressing mCD14, MD-2, and TLR4 by transferring endotoxin to mCD14, which then transfers endotoxin to endogenous wild-type MD-2·TLR4. These findings describe a novel pathway of endotoxin transfer that provides an additional layer of regulation of cell activation by endotoxin.

Received for publication, July 23, 2007 , and in revised form, October 12, 2007.

^* This work was supported by United States Public Health Service Grants AI59372 and PO144642 (to J. P. W.) and a Veterans' Administration Merit Review grant (to T. L. G.). 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 To whom correspondence should be addressed. Tel.: 319-335-4268; Fax: 319-335-4191; E-mail: jerrold-weiss{at}uiowa.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Teghanemt, R. L. Widstrom, T. L. Gioannini, and J. P. Weiss Isolation of Monomeric and Dimeric Secreted MD-2: ENDOTOXIN{middle dot}sCD14 AND TOLL-LIKE RECEPTOR 4 ECTODOMAIN SELECTIVELY REACT WITH THE MONOMERIC FORM OF SECRETED MD-2 J. Biol. Chem., August 8, 2008; 283(32): 21881 - 21889. [Abstract] [Full Text] [PDF]