Neutralization of thrombin by antithrombin III in the presence of cultured human fibroblasts.
Recent evidence suggests that heparan sulfate on endothelial cell surfaces acts as a catalyst for the neutralization of thrombin by antithrombin III (AT III). Fibroblasts also produce heparan sulfate which is present on the cell surface and secreted into the extracellular matrix. We evaluated the ability of cultured human fibroblasts to catalyze the interaction between thrombin and AT III and found that heparan sulfate produced by post-confluent fibroblasts was anticoagulantly active. Furthermore, after initial binding of thrombin to cells, thrombin-heparan sulfate appeared in the fluid phase above the cells; this thrombin could be rapidly neutralized by AT III independent of the further presence of cells. These results indicate that fibroblasts do produce an anticoagulantly active species of heparan sulfate and that the normal interaction between AT III and thrombin may be driven by initial release of heparan sulfate from the cell surface by thrombin followed by AT III interaction with the soluble thrombin-heparan sulfate complex.
Brandt
J T
JT
Department of Pathology, Ohio State University, Columbus 43210.
Stephens
R E
RE
Hinkle
G H
GH
D000990:Antithrombin III / Q000494:pharmacology*; D002384:Catalysis; D002462:Cell Membrane; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005966:Glucuronidase; D006025:Glycosaminoglycans / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000494:pharmacology; D019763:Heparin Lyase; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D010978:Platelet Factor 4 / Q000502:physiology; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*; D000099175:Heparanase
D000990:Antithrombin III; D005966:Glucuronidase; D006025:Glycosaminoglycans; D006026:Glycoside Hydrolases; D019763:Heparin Lyase; D006497:Heparan Sulfate; D010978:Platelet Factor 4; D011133:Polysaccharide-Lyases; D011479:Protamines; D013917:Thrombin; D000099175:Heparanase