Chloroquine and ammonium ion inhibit receptor-mediated endocytosis of mannose-glycoconjugates by macrophages: Apparent inhibition of receptor recycling

¹²⁵I-Mannose-BSA is taken up by macrophages by receptor-mediated pinocytosis. Previous studies indicated that uptake is rapid and proceeds linearly with time in the absence of protein synthesis suggesting that receptors are conserved and recycled. Chloroquine and NH₄⁺ inhibit uptake of ¹²⁵I-Mannose-BSA and its subsequent digestion by macrophages. Inhibition of uptake is inhibitor-concentration and time dependent. Both binding of ligand (4°) and internalization of pre-bound ligand (4°) following warm-up are unaffected by the inhibitors. However, brief incubation of cells at 37° with inhibitor in the absence of ligand results in a substantial reduction in cell surface binding sites. Our interpretation of these results is that chloroquine and NH₄⁺ inhibit receptor recycling and thereby inhibit ligand uptake.