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To characterize receptors for α interferon (IFN-α) on human cells, we studied the binding of radioiodinated recombinant DNA-derived human IFN-α to human peripheral blood mononuclear cells (PBMCs) from normal individuals and from patients with chronic type B hepatitis. At 1 ° C, binding reached equilibrium after 2 to 3 hours of incubation, and saturation of specific binding occurred at a concentration of approximately 4000 fmol/ml. Binding of labeled IFN-α was specific; it was inhibited by an excess of unlabeled IFN-α or IFN-β but not by cholera toxin or IFN-γ. Scatchard analysis of binding data yielded for normal PBMCs an apparent dissociation constant (Kd) of 1.54 ± 0.49 × 10−9 mol/L (mean ± SD) and an apparent maximum binding capacity (Bmax) of 7.35 ± 1.22 × 10−11 mol/L. Corresponding values for patients with chronic type B hepatitis who had not received treatment were similar, suggesting that such patients should respond normally to endogenous interferon. Analysis of data on the binding of labeled IFN-α to normal PBMCs from experiments in which a high specific activity ligand or subpopulations of PBMCs had been used revealed that receptors for IFN-α on PBMCs are heterogenous. In patients with chronic type B hepatitis who were receiving IFN-α therapy, the apparent Kd was increased (3.02 ± 0.91 × 10−9 mol/L) without any appreciable change in the apparent Bmax or any appreciable changes in the proportions of subpopulations of PBMCs. This decreased affinity induced by IFN-α treatment does not necessarily reflect an effect on a single binding site. A similar change in binding affinity occurred after preincubatlon of normal PBMCs with IFN-α at 37 ° C. These findings are compatible with IFN-α inducing changes in the plasma membrane or cytoskeleton of PBMCs or a selective loss of high-affinity binding sites on PBMCs.
Abbreviations:Bmax (maximum binding), HIV (human immunodeficiency virus), IFN-α (α interferon), Kd (dissociation constant), PBMC (peripheral blood mononuclear cell)
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Accepted: January 16, 1989
Received in revised form: January 13, 1989
Received: September 22, 1986
© 1989 Published by Elsevier Inc.