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Role of cellular receptors in regulation of fibrinolysis

Ewa Zastawna, Danuta Rość

CaseRepClinPractRev 2002; 3(3):187-193

ID: 474515


Cellular surface receptors play a special role in the plasminogen activation system. Some receptors, localizing plasminogen activators on the cell surface have profibrinolytic functions, while others mediate the clearance of
fibrinolytic system proteins. Plasminogen receptors are characterized by their relatively low affinity and high density on the surface of many cell types. Plasminogen receptors (enolase, annexin II) posses in their structure
C-terminal lysine groups and recognize lysine-binding sites in plasminogen molecules. Binding of plasminogen by cells results in enhanced plasmin generation and protection against inactivation of plasmin by inhibitors.
Annexin II occupies a particular position among the cell surface t-PA-binding receptors. The presence of this receptor has been demonstrated on the surface of vascular wall endothelial cells, platelets, neutrocytes, monocytes.
Formation of a tri-component complex – t-PA – annexin II – plasminogen enhances the catalytic capacity of the process of plasminogen activation by t-PA. Binding of a u-PA molecule to a specific uPAR receptor regulates its activity by the mechanism leading to u-PA transformation into an active form, or inhibiting u-PA activity by binding with specific inhibitors. The presence
of uPAR has been demonstrated on the surface of peripheral blood cells: monocytes, granulocytes, lymphocytes B, fibroblasts. Interaction of u-PA with the receptor involves it in the processes requiring extracellular proteolysis,
such as plasminogen activation, wound healing, neoplastic and non-neoplastic cell migration. Liver is the main organ responsible for the clearance of plasminogen activators. The essential role is played here
by the membranous receptor LRP localized on hepatocytes and Kupfer cells in the liver, responsible for the elimination of t-PA – PAI-1, u-PA – PAI-1, u-PA – PN-1 complexes, plasmin-α2-M complex and free molecules
of fibrinolytic system components from the circulation. Other structures involved in t-PA elimination include receptors recognizing t-pa carbohydrate residues, i.a. the mannose receptor localized on hepatic endothelial
cells.

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