Thromb Haemost 1988; 59(03): 480-484
DOI: 10.1055/s-0038-1647519
Original Article
Schattauer GmbH Stuttgart

Tissue Plasminogen Activator is Endocytosed by Mannose and Galactose Receptors of Rat Liver Cells

Bård Smedsrød
1  The Department of Medical and Physiological Chemistry, University of Uppsala, Sweden
,
Monica Einarsson
2  The Research Department Biochemistry, KabiVitrum AB, Stockholm, Sweden
,
Håkan Pertoft
1  The Department of Medical and Physiological Chemistry, University of Uppsala, Sweden
› Author Affiliations
Further Information

Publication History

Received 17 July 1987

Accepted after revision 19 February 1988

Publication Date:
29 June 2018 (online)

Summary

Experiments were carried out to charact erize the specificity of uptake of tPA in rat liver cells. Endocytosis in liver endothelial cells of the native carbohydrate variants of tissue plasminogen activator (tPA), and tPA inactivated by diisopropyl fluorophosphate was found to be competitive, suggesting that the determinant being recognized by these cells is different from the active site. Fibronectin and urokinase, which show partial homology with tPA, did not compete with tPA for uptake in liver endothelial cells. Hyaluronic acid, collagen, or IgG, which are endocytosed by specific receptors in liver endothelial cells, did not interfere with the uptake.

Reduced endocytosis by liver endothelial cells was observed with tPA modified in the carbohydrate side chains, suggesting that these structures are important for uptake. Ovalbumin, mannan, mannose, fructose, and EDTA, but not galactose, effectively inhibited uptake in liver endothelial cells of both native and diisopropyl fluorophosphate-inhibited tPA, but had very little effect on the uptake of tPA modified in the carbohydrate side chains.

Endocytosis of native tPA by parenchymal cells could be inhibited by galactose, ovalbumin, and EDTA, but not by mannose.

These results suggest that endocytosis of tPA by liver endothelial cells and parenchymal cells is mediated by the mannose and galactose receptors, respectively.