title: Hyaluronan oligosaccharides perturb lymphocyte slow rolling on brain vascular endothelial cells: implications for inflammatory demyelinating disease.
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.
authors: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave., Beaverton, OR 97006, USA.
authors: Clayton W
authors: CW
authors: Winkler
authors: Scott C
authors: SC
authors: Foster
authors: Asako
authors: A
authors: Itakura
authors: Steven G
authors: SG
authors: Matsumoto
authors: Akira
authors: A
authors: Asari
authors: Owen J T
authors: OJ
authors: McCarty
authors: Larry S
authors: LS
authors: Sherman
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology*; D036904:Leukocyte Rolling / Q000187:drug effects*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000473:pathology; D009844:Oligosaccharides / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D009844:Oligosaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D006820:Hyaluronic Acid