CELLULAR TARGETS AND RECEPTORS FOR INTERLEUKIN-6 .1. INVIVO AND INVITRO UPTAKE OF IL-6 IN LIVER AND HEPATOCYTES

Abstract. Interleukin‐6 (IL‐6) is a potent stimulator of the hepatic synthesis of acute‐phase proteins. 125I‐labelled IL‐6 disappeared from the blood of rats with an overall half‐time of about 1.5 min; 41% of the injected tracer dose was recovered in the liver by 15 min. The clearance was biphasic. The simultaneous injection of tracer and an excess of unlabelled IL‐6 eliminated the initial rapid phase, and reduced the hepatic uptake to 14%. Light microscopic autoradio‐graphy showed 5% of the grains over non‐hepatocytes, and 80% over hepatocytes, accumulating in areas around the bile canaliculi. Thereafter, degradation products accumulated in the bile. At 4d̀C, isolated rat hepatocytes bound IL‐6 with an apparent Kd of 39 pmol 1‐1 to a uniform class of 4500 receptors per cell with an apparent molar mass of 115–120 kg mol‐1. The HepG2 human hepatocellular cell line bound IL‐6 with an apparent Kd of 21 pmol 1‐1 to a uniform class of 1200 receptors per cell with an apparent molar mass of 155–160 kg mol‐1. At 37d̀C, both cell types endocytosed the bound ligand slowly, and degradation products appeared in the medium after a relatively long lag period (40 min in hepatocytes and 1 h in HepG2 cells)., Copyright © 1990, Wiley Blackwell. All rights reserved