Effects of fibroblasts and endothelial cells on inactivation of target proteases by protease nexin-1, heparin cofactor II, and C1-inhibitor.
Previous studies have shown that glycosaminoglycans in the extracellular matrix accelerate the inactivation of target proteases by certain protease inhibitors. It has been suggested that the ability of the matrix of certain cells to accelerate some inhibitors but not others might reflect the site of action of the inhibitors. Previous studies showed that fibroblasts accelerate the inactivation of thrombin by protease nexin-1, an inhibitor that appears to function at the surface of cells in extravascular tissues. The present experiments showed that endothelial cells also accelerate this reaction. The accelerative activity was accounted for by the extracellular matrix and was mostly due to heparan sulfate. Fibroblasts but not endothelial cells accelerated the inactivation of thrombin by heparin cofactor II, an abundant inhibitor in plasma. This is consistent with previous suggestions that heparin cofactor II inactivates thrombin when plasma is exposed to fibroblasts and smooth muscle cells. Neither fibroblasts nor endothelial cells accelerated the inactivation of C1s by plasma C1-inhibitor.
Hiramoto
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SA
Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine 92717.
Cunningham
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DD
D016564:Amyloid beta-Protein Precursor; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D003174:Complement C1 Inactivator Proteins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology*; D006026:Glycoside Hydrolases / Q000378:metabolism; D015844:Heparin Cofactor II; D006801:Humans; D011480:Protease Inhibitors / Q000502:physiology*; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D058258:Serpin E2
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D003174:Complement C1 Inactivator Proteins; D006023:Glycoproteins; D011480:Protease Inhibitors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C545486:SERPINE2 protein, human; D058258:Serpin E2; D015844:Heparin Cofactor II; D006026:Glycoside Hydrolases