Human hepatocytes exhibit receptors for α 2 ‐macroglobulin and pregnancy zone protein‐proteinase complexes

. Hepatocytes were isolated by application of the two‐step collagenase technique to pieces of human liver. 125 I‐labelled α 2 ‐macroglobulin‐trypsin complex bound to hepatocytes at 4°C with a half time of approximately 4·5 h. At near equilibrium half of the receptors were saturated at an α 2 ‐macroglobulin‐trypsin complex concentration of about 60 pmol l −1 and the Scatchard plot was linear. Dissociation of the labelled complex was slow (T½ = 24 h) at low receptor occupancies. At high receptor occupancies dissociation was biphasic with a rate constant ( K − 1) for the initial rapid phase of about 2·4 × 10 −2 min −1 . Labelled α 2 ‐macroglobulin‐trypsin complex bound at 4°C was rapidly internalized at 37°C (T½ = 1·9 min), and in 3·5 h approximately 10% of the label was released into the medium in a trichloroacetic acid‐soluble form. At 37°C, 125 Iα 2 ‐macroglobulin‐trypsin was taken up by hepatocytes and trichloroacetic acid soluble radioactivity appeared in the medium following a sigmoidal curve. Similar results were obtained with 125 I‐pregnancy zone protein‐chymotrypsin complex. At 4°C, hepatocytes bound nearly equal amounts of labelled α 2 ‐macroglobulin‐trypsin and pregnancy zone protein‐chymotrypsin complex, and a large excess (100 nmol l −1 ) of one of the macroglobulins could almost completely abolish binding of trace amounts (5−20 pmol l −1 ) of the other. The present findings strongly suggest that the hepatocyte is of major importance for removal of α 2 ‐macroglobulin‐ and pregnancy zone protein‐proteinase complex in humans, in agreement with previous results in rats and mice.