Gangliosides interact directly with plasminogen and urokinase and may mediate binding of these fibrinolytic components to cells.
Receptors for the fibrinolytic molecules plasminogen and urokinase are expressed at high capacity on a wide variety of peripheral blood cells and transformed cell lines. We have considered whether gangliosides, components of the outer leaflets of cell membranes, may modulate the interactions of these fibrinolytic ligands with cells. Radiolabeled plasminogen and urokinase bound directly to insolubilized gangliosides. The interactions were saturable and were 50% inhibited by 2.2 microM unlabeled plasminogen or 12 nM unlabeled urokinase, respectively. A panel of gangliosides inhibited binding of both ligands to U937 monocytoid cells, and the order of decreasing inhibitory effectiveness was GD1a greater than GM1 greater than GT1b greater than GM2, while GM3 was minimally effective. The individual components of gangliosides, hexoses, hexosamines, sialic acid, GM1 pentasaccharide, ceramides, and glucocerebrosides were ineffective in in inhibiting the binding of plasminogen and urokinase either to cells or to insolubilized gangliosides. Binding of both ligands to endothelial cells and granulocytes and binding of plasminogen to platelets were also inhibited by gangliosides. U937 cells were cultured with gangliosides to allow incorporation of these glycolipids into the cell membranes. After 3 days of culture, both urokinase binding and plasminogen binding to the cells became enhanced. These results suggest that gangliosides can directly bind to these fibrinolytic components and may mediate or modulate the interactions of plasminogen and urokinase with a variety of cell types.
Miles
L A
LA
Research Institute of Scripps Clinic, La Jolla, California 92037.
Dahlberg
C M
CM
Levin
E G
EG
Plow
E F
EF
D002241:Carbohydrates / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000494:pharmacology; D010958:Plasminogen / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D002241:Carbohydrates; D005732:Gangliosides; D008024:Ligands; D008055:Lipids; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator