THE HEPATIC ACUTE-PHASE PROTEINS ALPHA-1-ANTITRYPSIN AND ALPHA-2-MACROGLOBULIN INHIBIT BINDING OF TRANSFERRIN TO ITS RECEPTOR

Transferrin binding to human placental sites was inhibited by the acute-phase proteins alpha1-antitrypsin (alpha1-AT) and alpha2-macroglobulin (alpha2-MG), whereas haptoglobin, C-reactive protein and ferritin displayed no such effect. In equilibrium saturation binding assays, the effective acute-phase proteins decreased the apparent affinity of the binding sites for transferrin, but the transferrin binding-site density B(max.) was not significantly changed. For instance, the addition of 30 muM alpha1-AT increased the K(D) of transferrin from 8.46+/-1.51 nM to 21.6+/-3.04 nM; the B(max.) values were 1.17+/-0.18 pmol/mg of protein and 1.04+/-0.25 pmol/mg of protein respectively. In kinetic studies, alpha1-AT decreased the association rate constant k+1 of the I-125-transferrin-binding-site complex from 2.18(+/-0.21) x 10(7) M-1.min-1 to 3.99(+/-0.18) x 10(6) M-1.min-1. In contrast, the dissociation rate constant k-1 was not changed (0.0948+/-0.002 min-1, 0.089+/-0.0017 min-1). On isoelectric focusing, no alteration in transferrin protein pattern or shift in isoelectric point was detected in the presence of alpha1-AT. Inhibition of transferrin binding by the acute-phase proteins alpha1-AT and alpha2-MG is competitive. Interestingly, inhibition is already present at physiological concentrations. However, full inhibition is only achieved at concentrations above the normal range, which are attained in acute-phase reactions.