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This Article Full Text (PDF) 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nelson, R. M. Articles by Bevilacqua, M. P. Search for Related Content PubMed PubMed Citation Articles by Nelson, R. M. Articles by Bevilacqua, M. P. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Heparin oligosaccharides bind L- and P-selectin and inhibit acute inflammation RM Nelson, O Cecconi, WG Roberts, A Aruffo, RJ Linhardt and MP Bevilacqua Howard Hughes Medical Institute, University of California, San Diego, La Jolla. Initial attachment of leukocytes to the vessel wall at sites of inflammation is supported by a family of carbohydrate-binding adhesion molecules called the selectins. Selectin ligands include sialyl-Lewis x (sLex, Neu5Ac alpha 2-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc--) and related structures. We report here that defined heparin oligosaccharides interact with the selectins. Heparin chains containing four or more monosaccharide residues inhibited the function of L- and P-selectin, but not E-selectin, in vitro. In a competition enzyme-linked immunosorbent assay measuring inhibition of solution-phase selectin-Ig fusion proteins (selectin-Ig) binding to immobilized bovine serum albumin-sLex neoglycoprotein, a heparin-derived tetrasaccharide mixture inhibited 50% of L- and P-selectin-Ig binding (IC50) at 200 +/- 40 mumol/L and 850 +/- 110 mumol/L, respectively. A single hexasulfated tetrasaccharide (delta UA2S alpha 1-4GlcNS6S alpha 1-4IdoA2S alpha 1- 4GlcNS6S) was particularly active against L- and P-selectin-Ig (IC50 = 46 +/- 5 mumol/L and 341 +/- 24 mumol/L). By comparison, the tetrasaccharide sLex was not inhibitory at concentrations up to 1 mmol/L. In cell adhesion assays, heparin tetrasaccharides reduced binding of neutrophils to COS cells expressing P-selectin but not to COS cells expressing E-selectin. They also blocked colon cancer cell adhesion to L- and P-selectin but not E-selectin. In a model of acute inflammation, intravenously administered heparin tetrasaccharides diminished influx of neutrophils into the peritoneal cavities of thioglycollate-treated mice. We conclude that heparin oligosaccharides, including non-anticoagulant tetrasaccharides, are effective L- and P- selectin inhibitors in vitro and have anti-inflammatory activity in vivo. Volume 82, Issue 11, pp. 3253-3258, 12/01/1993 Copyright © 1993 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. N. Schilte, J. Loureiro, E. D. Keuning, P. M. t. Wee, J. W.A.M. Celie, R. H.J. Beelen, and J. van den Born LONG-TERM INTERVENTION WITH HEPARINS IN A RAT MODEL OF PERITONEAL DIALYSIS Perit. Dial. Int., January 1, 2009; 29(1): 26 - 35. [Abstract] [Full Text] [PDF] J. M. Gitlin, J. W. Homeister, J. Bulgrien, J. Counselman, L. K. Curtiss, J. B. Lowe, and W. A. Boisvert Disruption of Tissue-Specific Fucosyltransferase VII, an Enzyme Necessary for Selectin Ligand Synthesis, Suppresses Atherosclerosis in Mice Am. J. Pathol., January 1, 2009; 174(1): 343 - 350. [Abstract] [Full Text] [PDF] D. Y. Lee, K. Park, S. K. Kim, R.-W. Park, I. C. Kwon, S. Y. Kim, and Y. 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