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 alpha 1-antitrypsin (alpha 1-AT) and alpha 2-macroglobulin (alpha 2-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 Bmax. was not significantly changed. For instance, the addition of 30 microM alpha 1-AT increased the KD of transferrin from 8.46 +/- 1.51 nM to 21.6 +/- 3.04 nM; the Bmax. values were 1.17 +/- 0.18 pmol/mg of protein and 1.04 +/- 0.25 pmol/mg of protein respectively. In kinetic studies, alpha 1-AT decreased the association rate constant k+1 of the 125I-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 alpha 1-AT. Inhibition of transferrin binding by the acute-phase proteins alpha 1-AT and alpha 2-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.
Graziadei
I
I
Department of Internal Medicine, University of Innsbruck, Austria.
Kaserbacher
R
R
Braunsteiner
H
H
Vogel
W
W
D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D007525:Isoelectric Focusing; D007700:Kinetics; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011990:Receptors, Transferrin / Q000187:drug effects / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*; D000511:alpha-Macroglobulins / Q000494:pharmacology*
D007457:Iodine Radioisotopes; D011990:Receptors, Transferrin; D014168:Transferrin; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins