Versican interacts with chemokines and modulates cellular responses

We previously reported that versican, a large, chondroitin sulfate proteogl ycan, isolated from a renal adenocarcinoma cell line, ACHN, binds L-selecti n. Here we report that versican also binds certain chemokines and regulates chemokine function. This binding was strongly inhibited by the chondroitin ase digestion of versican or by the addition of soluble chondroitin sulfate (CS) B, CS E, or heparan sulfate. Furthermore, these glycosaminoglycans (G AGs) could bind directly to the chemokines that bind versican, Thus, versic an appears to interact with chemokines via its GAGs. We next examined if ve rsican or GAGs affect secondary lymphoid tissue chemokine (SLC)-induced int egrin activation and Ca2+ mobilization in lymphoid cells expressing a recep tor for SLC, CC chemokine receptor 7. Interestingly, whereas heparan sulfat e supported both alpha (4)beta (7) integrin-dependent binding to mucosal ad dressin cell adhesion molecule-1 (MAdCAM-1)-IgG and Ca2+ mobilization induc ed by SLC, versican or CS B inhibited these cellular responses, and the ext ent of inhibition was dependent on the dose of versican or CS B added. Thes e findings suggest that different proteoglycans have different functions in the regulation of chemokine activities and that versican may negatively re gulate the function of SLC via its GAG chains.