Mt. Nunez et al., INTESTINAL EPITHELIA (CACO-2) CELLS ACQUIRE IRON THROUGH THE BASOLATERAL ENDOCYTOSIS OF TRANSFERRIN, The Journal of nutrition, 126(9), 1996, pp. 2151-2158
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.