Mechanisms of lead transport in two intestinal epithelial cell lines

Abstract

Toxic effects of lead (Pb) have been recognized for as long as the heavy metal has been used in society; however, Pb toxicity is still a problem today in humans and animals. The primary targets of Pb toxicity are the hematological, renal and neurological systems. One of the best ways to prevent systemic Pb toxicity from an ingested source may be to reduce absorption of Pb from the gastrointestinal tract into the blood stream. Unfortunately, little is known about the mechanisms of Pb absorption through the intestinal epithelium. Using two established intestinal epithelial cell lines, IEC-6 and Caco-2, we studied the effects of temperature, metabolic inhibitors, sulfhydryl group modifiers, blocking of integrins with the tripeptide Arginine-Glycine-Aspartate (RGD), and induction of metallothionein by zinc on the total cellular accumulation of Pb. We have shown that the uptake of Pb into IEC-6 cells involves a potentially energy-independent pathway which may utilize sulfhydryl groups and integrins. We have also demonstrated that Pb is extruded from the IEC-6 cells by means of an energy-dependent mechanism. Additionally, in Caco-2 cells we demonstrated that induction of metallothionein by overnight exposure to zinc resulted in an increased total cellular Pb content, suggesting that metallothionein sequesters Pb in the cytosol. This is the first report of the use of intestinal epithelial cell lines to study the absorption of Pb. Understanding the mechanisms of Pb uptake will provide potential methods to prevent the absorption of ingested Pb into the systemic circulation.