Hyaluronan oligosaccharides perturb lymphocyte slow rolling on brain vascular endothelial cells: Implications for inflammatory demyelinating disease

Clayton W. Winkler, Scott C. Foster, Asako Itakura, Steven G. Matsumoto, Akira Asari, Owen J.T. McCarty, Larry S. Sherman

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Inflammatory demyelinating diseases like multiple sclerosis are characterized by mononuclear cell infiltration into the central nervous system. The glycosaminoglycan hyaluronan and its receptor, CD44, are implicated in the initiation and progression of a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Digestion of hyaluronan tethered to brain vascular endothelial cells by a hyaluronidase blocks the slow rolling of lymphocytes along activated brain vascular endothelial cells and delays the onset of EAE. These effects could be due to the elimination of hyaluronan or the generation of hyaluronan digestion products that influence lymphocytes or endothelial cells. Here, we found that hyaluronan dodecasaccharides impaired activated lymphocyte slow rolling on brain vascular endothelial cells when applied to lymphocytes but not to the endothelial cells. The effects of hyaluronan dodecasaccharides on lymphocyte rolling were independent of CD44 and a receptor for degraded hyaluronan, Toll-like receptor-4. Subcutaneous injection of hyaluronan dodecasaccharides or tetrasaccharides delayed the onset of EAE in a manner similar to subcutaneous injection of hyaluronidase. Hyaluronan oligosaccharides can therefore act directly on lymphocytes to modulate the onset of inflammatory demyelinating disease.

Original languageEnglish (US)
Pages (from-to)160-168
Number of pages9
JournalMatrix Biology
Volume32
Issue number3-4
DOIs
StatePublished - Apr 24 2013

Keywords

  • CD44
  • Endothelial cell
  • Hyaluronan
  • Myelin
  • Toll-like receptor

ASJC Scopus subject areas

  • Molecular Biology

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