Chondroitin Sulfate Structure Impacts its Immunological Effects on Murine Splenocytes Sensitized with Ovalbumin

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Akiyama, H.
Sakai, S.
Linhardt, Robert J.
Goda, Y.
Toida, T.
Maitani, T.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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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(β1-3)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.
Biochemical Journal, 382, 269-278
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Chondroitin Sulfate Structure Impacts its Immunological Effects on Murine Splenocytes Sensitized with Ovalbumin, H. Akiyama, S. Sakai, R. J. Linhardt, Y. Goda, T. Toida, T. Maitani, Biochemical Journal, 382, 269-278 2004.
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