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Title: Hepatic receptor(s) for serine protease-inhibitor complexes
Author: Combe, Caroline Jane
ISNI:       0000 0001 3561 0026
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1995
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A number of questions about the hepatic mechanisms of tissue-type plasminogen activator (t-PA) clearance still remain unanswered. Although certain liver endothelial cell receptors have been implicated, the parenchymal cell system, which is responsible for most clearance, still remains a mystery. The aim of this project, in the most simple terms, was to solve this mystery. The foundation upon which this project was built was that t-PA is cleared, by a hepatic receptor, in complex with its primary inhibitor, plasminogen activator inhibitor type 1 (PAI-1). The affinity of binding was estimated to be 0.8-1.0 nM and the number of binding sites per cell, 35 000-70 000. Affinity chromatography and chemical cross-linking resulted in a band of A?70 kDa which was presumed to be the receptor. This project was designed to characterize this hepatic receptor for t-PA-PAI-1 and determine whether plasmin-2-antiplasmin (PAP) is recognised by the same receptor. Characterizing the receptor was attempted initially by employing cell binding assays using the human hepatoma cell line, Hep G2. This methodology required the formation and characterization of pure pre-formed ligands which was achieved by overcoming preliminary problems. The binding assays showed that competition between t-PA-PAI-1 and PAP was occurring but that high non-specific binding and error between duplicate samples suggested that this system was not suitable for characterization of the receptor. The data accumulated in this study suggested that LRP was primarily responsible for hepatic uptake of t-PA and that proteases were recognised preferentially in complex with their inhibitors.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Liver; Fibrinolysis