INTESTINAL EPITHELIA (CACO-2) CELLS ACQUIRE IRON THROUGH THE BASOLATERAL ENDOCYTOSIS OF TRANSFERRIN

Although the absorption of iron through the intestinal epithelia is in versely related to body iron stores, the mechanisms by which the enter ocytes sense body iron stores are unknown. Polarized enterocytes have transferrin receptors in their basolateral surface; hence, we tested t he hypothesis that the endocytosis of circulating transferrin may be p art of the body's iron sensing mechanism. Particularly, we evaluated t he contribution of basolateral transferrin to iron content of intestin al cells, and we investigated what factors modulate this contribution. For this purpose, we used the intestinal cell line Caco-2 grown on po rous filters. When the cells were simultaneously offered equimolar amo unts of iron, from the apical medium as Fe-55-nitrilotriacetate and fr om the basolateral medium as Fe-59-transferrin, most of the internaliz ed iron came from the basolateral endocytosis of Fe-59-transferrin. Ex periments of transferrin binding and internalization showed that holot ransferrin and apotransferrin had similar numbers of basolateral recep tors. The receptors had associated constants for diferric transferrin, monoferric transferrin, and apotransferrin of 2.69, 1.71 and 0.26 x 1 0(7) L/mol, respectively. The binding of diferric transferrin or monof erric transferrin to receptors was competitively inhibited by apotrans ferrin. Caco-2 cells, but not K562 cells, showed inhibition of basolat eral, transferrin-mediated iron uptake by apotransferrin. This inhibit ion should regulate the net basolateral uptake of iron mediated by the endocytosis of Fe-containing transferrins. We propose that the basola teral endocytosis of transferrin forms part of the system by which int estinal epithelia cells sense plasma iron concentrations.