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  • Title: Chondroitin sulfate B exerts its inhibitory effect on secondary lymphoid tissue chemokine (SLC) by binding to the C-terminus of SLC.
    Author: Hirose J, Kawashima H, Swope Willis M, Springer TA, Hasegawa H, Yoshie O, Miyasaka M.
    Journal: Biochim Biophys Acta; 2002 Jul 03; 1571(3):219-24. PubMed ID: 12090936.
    Abstract:
    We previously reported that certain glycosaminoglycans (GAGs) bind secondary lymphoid tissue chemokine (SLC, CCL21) and that the SLC-binding GAGs, including chondroitin sulfate B (CS B), negatively modulate the function of SLC, although the mechanism remains unknown [J. Biol. Chem. 276 (2001) 5228]. To gain insight into the mechanism of inhibition, we used a C-terminally truncated SLC (SLC-T) that lacked clusters of basic amino acid residues that have been implicated in GAG binding. While SLC-T failed to bind any GAGs, it induced prominent intracellular Ca(2+) mobilization in CC chemokine receptor (CCR) 7-expressing cells, as did wild-type SLC. However, the SLC-T-induced Ca(2+) influx was not inhibited by CS B, unlike the SLC-induced Ca(2+) influx. These results demonstrate the requirement of the C-terminus of SLC for the inhibition of chemokine responses by CS B; that is, CS B exerts its inhibitory effect by binding to the C-terminus of SLC, thus defining the mode of action of CS B on certain chemokines.
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