%0 Journal Article %J Biochim. Biophys. Acta %D 2002 %T Chondroitin sulfate B exerts its inhibitory effect on secondary lymphoid tissue chemokine (SLC) by binding to the C-terminus of SLC %A Hirose, J. %A Kawashima, H. %A Willis, M. S. %A Springer, T.A. %A Hasegawa, H. %A Yoshie, O. %A Miyasaka, M. %X

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.

%B Biochim. Biophys. Acta %V 1571 %P 219-224 %G eng %N 3 %! Biochim. Biophys. Acta %F 445