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Abstract
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)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
January 16,
1989
Received in revised form:
January 13,
1989
Received:
September 22,
1986
Identification
Copyright
© 1989 Published by Elsevier Inc.
