Sulfated polysaccharide from the leaves of Artemisia princeps activates heparin cofactor II independently of the Lys(173) and Arg(189) residues of heparin cofactor II

A sulfated polysaccharide (AFE-HCD) purified from the leaves of Artemisia princeps Pamp selectively accelerated the rate of thrombin inhibition by heparin cofactor II (HCII). By using plasma derived HCII and bacterial expressed recombinant HCII molecules, the interaction between each HCII molecule and AFE-HCD was analyzed. AFE-HCD accelerated thrombin inhibition by plasma derived HCII or bacterial expressed wild type HCII to the same extent (IC50: 0.056 mu g/ml for plasma derived HCII and 0.066 mu g/ml for recombinant HCII under the experimental condition). The recombinant HCII (rHCII) molecule with Lys(173)-->Leu or Arg(189)-->His substitution, which is defective in interactions with heparin and dermatan sulfate, respectively, is activated by AFE-HCD to inhibit thrombin in a manner similar to wild type rHCII. These results suggested that activation of HCII was independent of its Lys(173) Or Arg(189) residue. Although AFE-HCD is a selective activator of HCII like dermatan sulfate, the amino acid residue required for the activation of HCII was distinct from that of dermatan sulfate as well as heparin. (C) 1997 Elsevier Science Ltd.