Affordable Access

deepdyve-link
Publisher Website

The heparan sulfate motif (GlcNS6S-IdoA2S)3, common in heparin, has a strict topography and is involved in cell behavior and disease.

Authors
  • Smits, Nicole C
  • Kurup, Sindhulakshmi
  • Rops, Angelique L
  • ten Dam, Gerdy B
  • Massuger, Leon F
  • Hafmans, Theo
  • Turnbull, Jeremy E
  • Spillmann, Dorothe
  • Li, Jin-ping
  • Kennel, Stephen J
  • Wall, Jonathan S
  • Shworak, Nicholas W
  • Dekhuijzen, P N Richard
  • van der Vlag, Johan
  • van Kuppevelt, Toin H
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry and Molecular Biology
Publication Date
Dec 24, 2010
Volume
285
Issue
52
Pages
41143–41151
Identifiers
DOI: 10.1074/jbc.M110.153791
PMID: 20837479
Source
Medline
License
Unknown

Abstract

Heparan sulfate (HS) is a structurally complex polysaccharide that interacts with a broad spectrum of extracellular effector ligands and thereby is thought to regulate a diverse array of biologic processes. The specificity of HS-ligand interactions is determined by the arrangement of sulfate groups on HS, which creates distinct binding motifs. Biologically important HS motifs are expected to exhibit regulated expression, yet there is a profound lack of tools to identify such motifs; consequently, little is known of their structures and functions. We have identified a novel phage display-derived antibody (NS4F5) that recognizes a highly regulated HS motif (HS(NS4F5)), which we have rigorously identified as (GlcNS6S-IdoA2S)(3). HS(NS4F5) exhibits a restricted expression in healthy adult tissues. Blocking HS(NS4F5) on cells in culture resulted in reduced proliferation and enhanced sensitivity to apoptosis. HS(NS4F5) is up-regulated in tumor endothelial cells, consistent with a role in endothelial cell activation. Indeed, TNF-α stimulated endothelial expression of HS(NS4F5), which contributed to leukocyte adhesion. In a mouse model of severe systemic amyloid protein A amyloidosis, HS(NS4F5) was expressed within amyloid deposits, which were successfully detected by microSPECT imaging using NS4F5 as a molecularly targeted probe. Combined, our results demonstrate that NS4F5 is a powerful tool for elucidating the biological function of HS(NS4F5) and can be exploited as a probe to detect novel polysaccharide biomarkers of disease processes.

Report this publication

Statistics

Seen <100 times