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dc.contributor.authorNelson, R.M.
dc.contributor.authorCecconi, O.
dc.contributor.authorRoberts, W.G.
dc.contributor.authorAruffo, A.
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorBevilacqua, M.P.
dc.identifier.citationHeparin Oligosaccharides Bind P- and L-Selectin and Inhibit Acute Inflammation, R.M. Nelson, O. Cecconi, W.G. Roberts, A. Aruffo, R.J. Linhardt, M.P. Bevilacqua, Blood, 82, 3253-3258 (1993).
dc.descriptionBlood, 82, 3253-3258
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractInitial 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.
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleHeparin Oligosaccharides Bind P- and L-Selectin and Inhibit Acute Inflammation
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)

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