thrombomodulin

Thrombomodulin, CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells.

The protein has a molecular mass of 74kDa, and consists of a single chain with 5 distinct domains.

It functions as a cofactor in the thrombin-induced activation of protein C in the anticoagulant pathway by forming a 1:1 stochiometric complex with thrombin. This raises the speed of protein C activation thousandfold. Thrombomodulin-bound thrombin has no procoagulant effect. The TT-complex also stimulates fibrinolysis by cleaving thrombin-activatable fibrinolysis inhibitor (TAFI) into its active form.

The antigen described as BDCA-3^[1] has turned out to be identical to thrombomodulin.^[2] Thus, it was revealed that this molecule also occurs on a very rare (0.02%) subset of human dendritic cells called MDC2. Its function on these cells is unknown at present, but apparently, thrombomodulin has at least one other ligand apart from thrombin, because anticoaglulation is a commonplace function, in contrast to the rarity of MDC2 cells.

References

1. ^ Dzionek, Andrzej; Fuchs,Anja; Schmidt, Petra; Cremer, Sabine; Zysk, Monika; Miltenyi, Stefan; Buck, David W. & Schmitz, Jürgen (2000): BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. Journal of Immuology 165(11): 6037-6046. PDF fulltext
2. ^ Dzionek, Andrzej; Inagaki, Yoshimasa; Okawa, Katsuya; Nagafune, Jun; Röck, Jürgen; Sohma, Yoshiaki; Winkels, Gregor; Zysk, Monika; Yamaguchi, Yasunori & Schmitz, Jürgen (2002): Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions, Human Immunology 63(12): 1133-1148. doi:10.1016/S0198-8859(02)00752-8 (HTML abstract)

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