Cellular targets and receptors for interleukin-6. II. Characterization of IL-6 binding and receptors in peripheral blood cells and macrophages.

Within 15 min, approximately 2.5% of 125I-labelled interleukin-6 (IL-6) injected intravenously into rats was taken up by the spleen. As determined by light microscopic autoradiography, uptake was mainly (60%) accounted for by macrophages in the red pulp. 125I-IL-6 binding in rat peritoneal macrophages was quantitatively similar to that in cultured human monocytes and T-cells. By comparison, IL-6 binding to polymorphonuclear granulocytes and freshly isolated monocytes was low. Stimulation with antigen, but not with mitogen (PWM), induced receptor presentation in B-cells, whereas antigen and mitogen downregulated the binding in T-cells. At 4 degrees C, labelled IL-6 bound to cells with a half-time of about 1.5 h. Binding appeared reversible, but dissociation was slow and incomplete. The apparent Kd for IL-6 binding was about 30 pmol l-1 in most cell types, however, values of approximately 120 pmol l-1 were obtained in polymorphonuclear granulocytes. At 37 degrees C, 125I-IL-6 was rapidly internalized by T-cells and monocyte-macrophages, and after a lag time, TCA-soluble radioactivity was released from the cells following a sigmoidal curve. Polyacrylamide gel electrophoresis of radiolabelled IL-6 cross-linked to its binding sites in T-cells, yielded receptor-ligand complexes with molar masses of 70-80 and 120-140 kg mol-1. This would agree with a dimeric conformation of the IL-6 receptor.