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

J. Biol. Chem., Vol. 275, Issue 44, 34818-34825, November 3, 2000

This Article Full Text Full Text (PDF) All Versions of this Article: 275/44/34818    most recent M001257200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xie, X. Articles by Spertini, O. Search for Related Content PubMed PubMed Citation Articles by Xie, X. Articles by Spertini, O. Social Bookmarking                      What's this?

Inhibition of Selectin-mediated Cell Adhesion and Prevention of Acute Inflammation by Nonanticoagulant Sulfated Saccharides
STUDIES WITH CARBOXYL-REDUCED AND SULFATED HEPARIN AND WITH TRESTATIN A SULFATE^*

Xun Xie^§, Anne-Sophie Rivier^§, Andreas Zakrzewicz^¶, Michael Bernimoulin, Xian-Lu Zeng, Hans Peter Wessel, Marc Schapira, and Olivier Spertini^**

From the  Division and Central Laboratory of Hematology, Centre Hospitalier Universitaire Vaudois, Bugnon 46, 1011 Lausanne, Switzerland, the ^¶ Institute of Physiology, Freie Universität, Berlin, Arnimallee 22, 14195 Berlin, Germany, and the  Pharmaceutical Research Department, Building 15/30F, Hoffmann-La Roche Ltd., 4002 Basel, Switzerland

Selectins play a major role in the inflammatory reaction by initiating neutrophil attachment to activated vascular endothelium. Some heparin preparations can interact with L- and P-selectin; however, the determinants required for inhibiting selectin-mediated cell adhesion have not yet been characterized. We now report that carboxyl-reduced and sulfated heparin (prepared by chemical modifications of porcine intestinal mucosal heparin leading to the replacement of carboxylates by O-sulfate groups) and trestatin A sulfate (obtained by sulfation of trestatin A, a non-uronic pseudo-nonasaccharide extracted from Streptomyces dimorphogenes) exhibit strong anti-P-selectin and anti-L-selectin activity while lacking antithrombin-mediated anticoagulant activity. In vitro experiments revealed that both compounds inhibited P-selectin- and L-selectin-mediated cell adhesion under laminar flow conditions. Moreover, carboxyl-reduced and sulfated heparin and trestatin A sulfate were also active in vivo, as assessed by experiments showing 1) that microinfusion of trestatin A sulfate reduced by 96% leukocyte rolling along rat mesenteric postcapillary venules and 2) that both compounds inhibited (by 58-81%) neutrophil migration into thioglycollate-inflamed peritoneum of BALB/c mice. These results indicate that nonanticoagulant sulfated saccharides targeted at P-selectin and L-selectin may have therapeutic potential in inflammatory disorders.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				C. Tauxe, X. Xie, M. Joffraud, M. Martinez, M. Schapira, and O. Spertini P-selectin Glycoprotein Ligand-1 Decameric Repeats Regulate Selectin-dependent Rolling under Flow Conditions J. Biol. Chem., October 17, 2008; 283(42): 28536 - 28545. [Abstract] [Full Text] [PDF]

				M. Schouten, W. J. Wiersinga, M. Levi, and T. van der Poll Inflammation, endothelium, and coagulation in sepsis J. Leukoc. Biol., March 1, 2008; 83(3): 536 - 545. [Abstract] [Full Text] [PDF]

				C. Abbal, M. Lambelet, D. Bertaggia, C. Gerbex, M. Martinez, A. Arcaro, M. Schapira, and O. Spertini Lipid raft adhesion receptors and Syk regulate selectin-dependent rolling under flow conditions Blood, November 15, 2006; 108(10): 3352 - 3359. [Abstract] [Full Text] [PDF]

				J. L. Stevenson, S. H. Choi, and A. Varki Differential Metastasis Inhibition by Clinically Relevant Levels of Heparins--Correlation with Selectin Inhibition, Not Antithrombotic Activity Clin. Cancer Res., October 1, 2005; 11(19): 7003 - 7011. [Abstract] [Full Text] [PDF]

				M. Martinez, M. Joffraud, S. Giraud, B. Baisse, M. P. Bernimoulin, M. Schapira, and O. Spertini Regulation of PSGL-1 Interactions with L-selectin, P-selectin, and E-selectin: ROLE OF HUMAN FUCOSYLTRANSFERASE-IV AND -VII J. Biol. Chem., February 18, 2005; 280(7): 5378 - 5390. [Abstract] [Full Text] [PDF]

				C. Zaph and P. Scott Th1 Cell-Mediated Resistance to Cutaneous Infection with Leishmania major Is Independent of P- and E-Selectins J. Immunol., November 1, 2003; 171(9): 4726 - 4732. [Abstract] [Full Text] [PDF]

				M. GOTTE Syndecans in inflammation FASEB J, April 1, 2003; 17(6): 575 - 591. [Abstract] [Full Text] [PDF]

				M. P. Bernimoulin, X.-L. Zeng, C. Abbal, S. Giraud, M. Martinez, O. Michielin, M. Schapira, and O. Spertini Molecular Basis of Leukocyte Rolling on PSGL-1. PREDOMINANT ROLE OF CORE-2 O-GLYCANS AND OF TYROSINE SULFATE RESIDUE 51 J. Biol. Chem., January 3, 2003; 278(1): 37 - 47. [Abstract] [Full Text] [PDF]