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Thromb Haemost 1992; 68(06): 737-743
DOI: 10.1055/s-0038-1646353
Original Article
Schattauer GmbH Stuttgart

Antibodies to Thrombomodulin Induce Receptor-Mediated Endocytosis in Human Saphenous Vein Endothelial Cells

Christine Brisson
INSERM U.311, Biologie et Pharmacologie des Interactions du Sang avec les Vaisseaux et les Biomatériaux, Strasbourg, France
,
Gisèle Archipoff
INSERM U.311, Biologie et Pharmacologie des Interactions du Sang avec les Vaisseaux et les Biomatériaux, Strasbourg, France
,
Marie-Louise Hartmann
INSERM U.311, Biologie et Pharmacologie des Interactions du Sang avec les Vaisseaux et les Biomatériaux, Strasbourg, France
,
Daniel Hanau
*   Laboratoire d’Histocompatibilité, Centre Régional de Transfusion Sanguine, Strasbourg, France
,
Alain Beretz
INSERM U.311, Biologie et Pharmacologie des Interactions du Sang avec les Vaisseaux et les Biomatériaux, Strasbourg, France
,
Jean-Marie Freyssinet
INSERM U.311, Biologie et Pharmacologie des Interactions du Sang avec les Vaisseaux et les Biomatériaux, Strasbourg, France
,
Jean-Pierre Cazenave
INSERM U.311, Biologie et Pharmacologie des Interactions du Sang avec les Vaisseaux et les Biomatériaux, Strasbourg, France
› Author Affiliations
Further Information

Publication History

Received 10 April 1992

Accepted after revision 02 July 1992

Publication Date:
04 July 2018 (online)

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Summary

The membrane glycoprotein thrombomodulin (TM) is an essential endothelial cell (EC) cofactor, which forms a 1:1 stoichiometric complex with thrombin. Binding of thrombin to the high affinity TM receptor transforms its procoagulant activity into an anticoagulant potential, by activating protein C. The fate of TM in the presence of thrombin is still unclear: some authors claim that the thrombin-TM complex is internalized in EC, while others find this complex to be stable for at least 2 h at 37° C on the EC surface. In the present study, we investigated the interactions of thrombin and Fab-fragments of anti-TM antibodies, coupled to 5 or 15 nm gold particles with saphenous vein endothelial cells. Our results demonstrate that TM can be observed both on the plasma membrane and in coated structures only in the presence of anti-TM antibodies. Addition of thrombin decreased the extent of this labeling, while in double labeling experiments, where cells were incubated with 5 nm gold coupled thrombin and 15 nm gold coupled Fab fragments of anti-TM antibodies, thrombin was cointernalized only when anti-TM antibodies were present. These results show that thrombin-TM complex is not significantly internalized in EC. The internalization of this complex induced by anti-TM antibodies could play an important role in the thrombotic complications induced by anti-EC autoantibodies.

 

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