Clearance receptors for tissue-type plasminogen activator

Hepatic clearance is one of the principal mechanisms regulating plasma concentrations of tissue-type plasminogen activator (t-PA). Two distinct pathways appear to be involved. Liver endothelial cells and Kupffer cells clear t-PA via the mannose receptor, whereas parenchymal cells clear t-PA via the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2-MR). This review presents the structural determinants on the t-PA molecule that mediate clearance via these two pathways, gives an overview of the structure of the LRP/alpha 2-MR and discusses the role of plasminogen activator inhibitor type 1 (PAI-1) in the hepatic clearance of t-PA.