DIFFERENTIAL RECOGNITION OF ALPHA(1)-ANTITRYPSIN-ELASTASE AND ALPHA(1)-ANTICHYMOTRYPSIN-CATHEPSIN-G COMPLEXES BY THE LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN

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, alpha(1)-antitrypsin-neutrophil elastase (alpha(1)AT-NEL) and alpha(1)-antichymotsypsin-cathepsin G (alpha(1)ACT-CathG) by normal murine fibroblasts (MEF) expressing LRP, and by a mutant fibroblast cell line (PEA13) which is genetically deficient for LRP, alpha(1)AT-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 alpha(1)AT-NEL complexes, In contrast to alpha(1)AT-NEL, MEF cells did not degrade alpha(1)ACT-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 alpha(1)ACT-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.