Inhibition of P-selectin-mediated inflammation cell adhesion by 6SCM-chitin

Here, we prepared several derivatives of chitin and detected their activities in blocking P-selectin-mediated inflammation cell (HL60 cell) adhesion. Our results showed that 6-O-sulfated chitin (6S-chitin) and 6-O-sulfated carboxymethyl chitin (6SCM-chitin), but not 6-O-carboxymethyl chitin (6CM-chitin), dramatically reduced P-selectin-mediated HL60 cell adhesion under static and flow conditions. Interestingly, 6SCM-chitin demonstrated stronger activity than 6S-chitin. Because 6SCM-chitin is obtained by the introduction of carboxymethyl group to C6 of 6S-chitin, we speculate that the synergy of sulfate and carboxymethyl groups in chitin might be indispensable for blocking P-selectin-mediated cell adhesion. The spacing arrangement of sulfate groups and carboxymethyl groups of modified chitin most probably meets the requirement of recognition by P-selectin. Our findings have a potential value for exploiting the biological use of chitin, especially for designing anti-inflammatory agents targeting P-selectin.

► We find that 6S-chitin inhibits P-selectin-mediated inflammation cell adhesion. ► Introduction of carboxymethyl groups enhances the effect of 6S-chitin. ► The synergy of 6-O-sulfation and carboxymethyl is required for blocking P-selectin.