Binding of α 2-macroglobulin to hepatocytes: Mechanism of in vivo clearance

Abstract

The binding of 125I-labeled human α 2-macroglobulin-methylamine to adult rat hepatocytes in primary culture was studied at 4°C. Cells which had been in culture for 4 hours exhibited steady state ligand binding after 1 hour, a receptor number of 22,400 receptors per cell, and a dissociation constant of 0.6 nM. Adult rat hepatocytes exhibited a significant decrease in receptor number with increased time in primary culture with less than 10% of the initial number of receptors remaining after 2 days (p <0.01). In autopsy studies of mice injected intravenously with 125I-labeled α 2-macroglobulin-methylamine, greater than 90% of the cleared ligand was found in the liver. Autoradiography of the liver demonstrated that 80% of the ligand was cleared by hepatocytes. It is concluded that the hepatocytes are the primary pathway for clearance from the circulation of receptor recognized α 2-macroglobulin.