ANALYSIS OF CD44 INTERACTIONS WITH HYALURONAN IN MURINE L CELL-FIBROBLASTS DEFICIENT IN GLYCOSAMINOGLYCAN SYNTHESIS - A ROLE FOR CHONDROITIN SULFATE

CD44 is a widely expressed cell adhesion molecule that binds the extra cellular matrix component, hyaluronan, in a tightly regulated manner, Previous studies have shown that the CD44-hyaluronan interaction is af fected by changes in the glycosylation state of CD44. In this study, w e take advantage of several well-characterized murine L cell mutants d efective in heparan sulfate synthesis (gro2C cells), heparan sulfate a nd chondroitin sulfate synthesis (sog9 cells), and glycosaminoglycan a nd oligosaccharide processing (sog8 cells) to assess the effects of th ese defects on the hyaluronan binding ability of CD44. In parental L c ells and gro2C cells, CD44 was induced to bind hyaluronan after additi on of the activating, anti-CD44 monoclonal antibody, IRAWB 14. By cont rast, no inducible binding was observed in sog9 cells, Treatment of L cells with sodium chlorate, an inhibitor of sulfation, also abolished inducible hyaluronan binding, However, inducible and some constitutive hyaluronan binding was observed in sog8 cells, This indicates that su lfation and, in particular, the addition of chondroitin sulfate are re quired for inducible hyaluronan binding by CD44 in L cells, However, i n the absence of fully processed oligosaccharides, chondroitin sulfate is not essential for hyaluronan binding, indicating that the effect o f chondroitin sulfate is dependent upon the glycosylation state of the cell, Thus, in addition to glycosylation, chondroitin sulfate biosynt hesis is an important post-translational modification that can affect the hyaluronan binding ability of CD44.