Fig. 3.

The non-oxidizable 3S mutant interacts directly with CXCR4. Fr-HMGB1 interacts with CXCL12 to promote cell migration and proliferation via CXCR4. A blocking antibody to CXCL12 or the CXCR4/CXCL12 inhibitor AMD3100 as well as the presence of H₂O₂ abolish fr-HMGB1 activities. On the contrary, 3S binds directly to CXCR4 in a CXCL12-independent manner and is more effective that fr-HMGB1 in inducing fibroblast migration mediated by Src activation and myoblast proliferation. It is likely that 3S recognizes a different site in the receptor compared to CXCL12, since neither AMD3100 nor an anti-CXCL12 antibody effectively block 3S-induced migration. Since 3S cannot be converted to oxidized HMGB1 forms, its chemotactic activity lasts in the presence of H₂O₂