Year: 1977
Type: conference-paper
Abstract: Vascular endothelial cells derived from rabbit vena cava and maintained in continuous culture retained properties characteristic of intact endothelium and were employed to characterize its fibrinolytic components. Cells growing on 125I-fibrin-coated petri dishes synthesized and secreted both: a) a plasminogen activator (PA) and, b) an inhibitor of fibrinolysis. Cell fractionation studies revealed that all PA was associated with a membrane fraction, while the inhibitor appeared to exist free in the cytosol. The PA was active following SDS-polyacrylamide gel electrophoresis and migrated as a single molecular species with a mol. wt. ~50,000. Similar activity and mol. wt. profiles were obtained when intact tissues (superior vena cava, aorta and kidney) and urine were extracted and analyzed. The inhibitor was inactivated upon brief exposure to mildly acidic conditions and had a mol. wt. ~80,000. The cells respond to external stimuli (phorbol-myristate-ester) by increased production of both activator and inhibitor, suggesting that the synthesis of these molecules is coordinate regulated. The response is rapid with intracellular changes often apparent within 1-2 hours, and is initiated at the level of gene expression. Changes in extracellular activities appeared 6-8 hours later. The presence of both a PA molecule and a fibrinolytic inhibitor within the same cell, although restricted to different cellular compartments, introduces a previously unappreciated level of complexity to cellular fibrinolytic phenomena and raises difficulties for the interpretation of observations concerning the presence or absence of PA in tissues.
Source: Thrombosis and Haemostasis
Authors: D.J. Loskutoff, T.S. Edgington
Institution: Scripps Clinic
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2946368932