Human fibroblasts accelerate the inhibition of thrombin by protease nexin.
Protease nexin (PN) is a protein protease inhibitor secreted by human fibroblasts in culture that complexes and inhibits certain regulatory serine proteases. The PN-protease complexes then bind to these cells and are rapidly internalized and degraded. This report shows that the fibroblast surface accelerates the formation of PN-thrombin complexes. In contrast, it did not accelerate the formation of complexes between thrombin and antithrombin III, a closely related protease inhibitor found in plasma. These results support a role for PN in the regulation of certain proteases in the extravascular compartment at and near the surface of tissue cells. The activity that accelerated PN-thrombin complex formation was membrane-associated, since fixed cells, purified membranes, and extracellular matrix preparations all contained this activity. The ability of cells to accelerate the reaction between PN and thrombin was inhibited by protamine, suggesting that the activity was similar to that of heparin. Heparitinase digestion of plasma membranes prior to assay reduced the activity by about 80%, suggesting that heparan sulfate may account for most of the accelerative activity.
Farrell
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Cunningham
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D016564:Amyloid beta-Protein Precursor; D000990:Antithrombin III / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000378:metabolism*; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013917:Thrombin / Q000037:antagonists & inhibitors*
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D011479:Protamines; D011480:Protease Inhibitors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D000990:Antithrombin III; D013917:Thrombin; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase