Endocytosis-Mediated Transport of Pb in Rat Blood Cells

Blood is an important reservoir for Pb storage in living organisms, and the storage of Pb in blood cells inhibits its discharge from blood. However, the mechanism and molecular targets of Pb entry and exit from blood cells have not been elucidated, which is the major barrier to reducing blood Pb levels in normal human beings. In this study, we explored the effect of Pb-binding proteins on blood Pb levels in rats at environmentally relevant concentrations (0.32 μg/g) by identifying the functions of Pb-binding proteins and validating them with inhibitors. The results showed that Pb-binding proteins in blood cells were mainly related to phagocytosis, while in plasma, they were mainly involved in the regulation of endopeptidase activity. Meanwhile, at the normal population Pb levels, endocytosis inhibitors, endopeptidase activity inhibitors, and coadministration of both can reduce the level of Pb in MEL (mouse erythroleukemia cells) cells by up to 50, 40, and 50%, respectively, while in rat blood, the reduction can reach up to 26, 13, and 32%, respectively. Collectively, these findings reveal that endocytosis increases blood Pb levels and provides a possible molecular target for Pb excretion at ambient concentrations.