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Clearance receptors for tissue-type plasminogen activator

C Camani1, E K Kruithof

  • 1Department of Medicine, University Hospital CHUV, Lausanne, Switzerland.

International Journal of Hematology
|August 1, 1994
PubMed
Summary

The liver clears tissue-type plasminogen activator (t-PA) through two main pathways: the mannose receptor on liver endothelial and Kupffer cells, and the LRP/alpha 2-MR on parenchymal cells. This review details t-PA structural factors influencing these clearance mechanisms.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Physiology

Background:

  • Hepatic clearance is a primary regulator of plasma concentrations of tissue-type plasminogen activator (t-PA).
  • Two distinct cellular pathways are implicated in t-PA hepatic uptake.
  • Liver endothelial cells and Kupffer cells utilize the mannose receptor, while parenchymal cells employ the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2-MR).

Purpose of the Study:

  • To review the structural determinants on the t-PA molecule responsible for mediating clearance via the mannose receptor and LRP/alpha 2-MR pathways.
  • To provide an overview of the structure and function of the LRP/alpha 2-MR.
  • To discuss the influence of plasminogen activator inhibitor type 1 (PAI-1) on hepatic t-PA clearance.

Main Methods:

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  • Literature review of studies on t-PA structure and hepatic clearance mechanisms.
  • Analysis of structural features of t-PA involved in receptor-mediated endocytosis.
  • Examination of the LRP/alpha 2-MR structure and its role in t-PA binding and uptake.

Main Results:

  • Specific structural regions of t-PA mediate its recognition by the mannose receptor and LRP/alpha 2-MR.
  • The LRP/alpha 2-MR is a multifunctional endocytic receptor crucial for clearing various ligands, including t-PA.
  • PAI-1 binding to t-PA may modulate its hepatic clearance, although the precise mechanisms require further elucidation.

Conclusions:

  • Hepatic clearance of t-PA is a complex process involving multiple receptor systems.
  • Understanding the structural basis of t-PA-receptor interactions is key to comprehending its pharmacokinetic profile.
  • The interplay between t-PA, its inhibitors, and hepatic receptors significantly impacts t-PA levels and function.