Chondroitin sulphate structure affects its immunological activities on murine splenocytes sensitized with ovalbumin.
Chondroitin sulphate (CS) is a glycosaminoglycan widely distributed in animal tissues, which has anti-inflammatory and chondroprotective properties. We reported previously that chondroitin 4-sulphate (CS-A) up-regulates the antigen-specific Th1 immune response of murine splenocytes sensitized with ovalbumin in vitro, and that CS suppresses the antigen-specific IgE responses. We now demonstrate that a specific sulphation pattern of the CS polysaccharide is required for the Th1-promoted activity, as other polysaccharides such as dextran and dextran sulphate do not significantly induce this activity. While the presence of some O-sulpho groups appear to be essential for activity, CS-A, and synthetically prepared, partially O-sulphonated CS, induce higher Th1-promoted activity than synthetically prepared, fully O-sulphonated CS. CS-A induces an activity greater than chondroitin sulphate B (CS-B) or chondroitin 6-sulphate (CS-C). In addition, chondroitin sulphate E (CS-E) induces greater activity than CS-A or CS-D. These results suggest that the GlcA(beta1-3)GalNAc(4,6-O-disulpho) sequence in CS-E is important for Th1-promoted activity. Furthermore, rat anti-mouse CD62L antibody, an antibody to L-selectin, inhibits the Th1-promoting activity of CS. These results suggest that the Th1-promoted activity could be associated with L-selectin on lymphocytes. These findings describe a new mechanism for the anti-inflammatory and chondroprotective properties of CS that may be useful in designing new therapeutic applications for CS used in the treatment of immediate-type hypersensitivity.
Akiyama
Hiroshi
H
National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158-8501 Japan. akiyama@nihs.go.jp
Sakai
Shinobu
S
Linhardt
Robert J
RJ
Goda
Yukihiro
Y
Toida
Toshihiko
T
Maitani
Tamio
T
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D011134:Polysaccharides / Q000378:metabolism / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology; D013154:Spleen / Q000166:cytology* / Q000502:physiology*; D013455:Sulfur / Q000378:metabolism / Q000494:pharmacology; D018417:Th1 Cells / Q000502:physiology
D016207:Cytokines; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D013455:Sulfur; D010047:Ovalbumin; D002809:Chondroitin Sulfates