Human fibroblasts accelerate the inhibition of thrombin by protease nexin

David Farrell, D. D. Cunningham

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6858-6862
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number18
StatePublished - 1986
Externally publishedYes

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Protease Nexins
Thrombin
Fibroblasts
heparitinsulfate lyase
Protease Inhibitors
Peptide Hydrolases
Cell Membrane
Protamines
Heparitin Sulfate
Serine Proteases
Extracellular Matrix
Heparin
Digestion
Membranes

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Human fibroblasts accelerate the inhibition of thrombin by protease nexin. / Farrell, David; Cunningham, D. D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 83, No. 18, 1986, p. 6858-6862.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Cunningham, D. D.

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AB - 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.

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