Differential recognition of α1-antitrypsin-elastase and α1-antichymotrypsin-cathepsin G complexes by the low density lipoprotein receptor-related protein

Wolfgang Poller, Thomas E. Willnow, Jan Hilpert, Joachim Herz

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Two multifunctional receptors, low density lipoprotein receptor-related protein (LRP) and gp330, have been implicated in the cellular uptake and degradation of a wide spectrum of functionally diverse ligands including plasma lipoproteins, proteases, and proteinase-inhibitor complexes. The two receptors show distinct tissue-specific expression patterns, suggesting different physiological functions. We have examined the cellular degradation of two serine proteinase inhibitor (serpin)-protease complexes, α1-antitrypsin-neutrophil elastase (α1AT·NEL) and α1-antichymotrypsin-cathepsin G (α1ACT·CathG) by normal murine fibroblasts (MEF) expressing LRP, and by a mutant fibroblast cell line (PEA13) which is genetically deficient for LRP. α1AT·NEL complexes bound to LRP on ligand blots and were degraded efficiently by the MEF cells, but not by PEA13 cells. Degradation of the complexes was also significantly reduced by antibodies directed against LRP, further suggesting that fibroblasts require LRP for the cellular uptake and degradation of α1AT·NEL complexes. In contrast to α1AT·NEL, MEF cells did not degrade α1ACT·CathG complexes. However, these complexes were rapidly degraded by the rat embryonal carcinoma cell line L2p58 which abundantly expresses gp330, raising the possibility that the α1ACT·CathG complex might be recognized by gp330. Both complexes were efficiently metabolized by the hepatoma cell line HepG2, presumably involving the serpin-enzyme complex receptor. The differential recognition of serpin-protease complexes by fibroblasts and hepatoma cells, however, indicates that LRP, gp330, and the serpin-enzyme complex receptor are distinct proteins.

Original languageEnglish (US)
Pages (from-to)2841-2845
Number of pages5
JournalJournal of Biological Chemistry
Volume270
Issue number6
DOIs
StatePublished - Feb 10 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Differential recognition of α<sub>1</sub>-antitrypsin-elastase and α<sub>1</sub>-antichymotrypsin-cathepsin G complexes by the low density lipoprotein receptor-related protein'. Together they form a unique fingerprint.

Cite this