The effect of human thrombomodulin on the inactivation of thrombin by human antithrombin III.
The effect of human thrombomodulin (TM) on the inactivation of thrombin by human antithrombin III (ATIII) was evaluated in comparison with that produced from rabbits. Human TM did not accelerate the thrombin inhibition by ATIII but rabbit TM enhanced the activity of ATIII. Also inclusion of human TM at increasing concentration suppressed the thrombin inhibitory activity of ATIII. The intensity of ATIII activity in the presence of heparin (0.01U/ml) was also diminished by the human TM. However, this ATIII- heparin cofactor activity recovered with the addition of a 10-fold amount of heparin (0.1U/ml). In SDS-polyacrylamide gel electrophoresis and immunoblotting analysis, we found a complex formation of ATIII with both human and rabbit TM (and further confirmed their presence with isoelectrofocusing electrophoresis- data not shown). These results indicate that human TM is substantially different from rabbit TM. Our results suggest that human TM show the crucial role on protein C activation system via thrombin.
Hirahara
K
K
Pharma Research Laboratories, Hoechst Japan Limited, Saitama.
Koyama
M
M
Matsuishi
T
T
Kurata
M
M
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism / Q000494:pharmacology*; D002852:Chromatography, Ion Exchange; D005260:Female; D006801:Humans; D010920:Placenta / Q000032:analysis; D011247:Pregnancy; D011486:Protein C / Q000378:metabolism; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D018179:Receptors, Thrombin; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D011486:Protein C; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D000990:Antithrombin III; D013917:Thrombin