Cellular targets and receptors for interleukin-6. I. In vivo and in vitro uptake of IL-6 in liver and hepatocytes.
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 autoradiography 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 4 degrees C, isolated rat hepatocytes bound IL-6 with an apparent Kd of 39 pmol l-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 l-1 to a uniform class of 1200 receptors per cell with an apparent molar mass of 155-160 kg mol-1. At 37 degrees C, 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).
Sonne
O
O
Institute of Physiology, University of Aarhus, Denmark.
Davidsen
O
O
Møller
B K
BK
Munck Petersen
C
C
D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D010477:Perfusion; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000032:analysis*; D019947:Receptors, Interleukin-6
D015850:Interleukin-6; D007457:Iodine Radioisotopes; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6