REGULATION OF FE ABSORPTION BY CULTURED INTESTINAL EPITHELIA (CACO-2)CELL MONOLAYERS WITH VARIED FE STATUS

Body Fe homeostasis is maintained through the regulation of Fe absorpt ion by the intestinal epithelia. Working under the hypothesis that the intracellular concentration of Fe is instrumental in the control of i ts transepithelial flux, we investigated in vitro which steps in Fe ab sorption are regulated by cellular Fe content-For that-study, Caco-2 c ells containing different concentrations of intracellular Fe-55 were g rown in porous filters, and the apical-to-cell-to-basolateral flux of Fe-59 was then determined. We found that 1) at low (up to 0.1 mM) intr acellular Fe content-the apical-to-basal Fe transport was primarily re gulated by a decrease in apical Fe uptake (first stage of regulation), 2) at higher levels of intracellular Fe (0.1-1 mM) the transepithelia l Fe flux was regulated by intracellular factors that sequester most o f the Fe taken up at the apical surface (second stage of regulation), and 3) a fraction of the apical-to-basolateral Fe flux was not regulat ed by the intracellular concentration of Fe. Ferritin synthesis preced ed the onset of the second stage of regulation, suggesting a causal re lationship between intracellular Fe levels, ferritin levels, and regul ation of Fe absorption.