Potential Immunomodulatory Role of Lead in Monocyte/Macrophage Differentiation

Lead (Pb) is a pernicious toxic metal and public health hazard, as it persists in the environment contaminating soil, food, and drinking water. Lead exerts its toxic effect on numerous organ systems, with the abundance of focus on the red blood cells and neurons of the hematopoietic and central nervous systems. However, insufficient investigation has been conducted on the effect of Pb on immune cells. In the current study, the toxic effects of Pb on immune cells of monocyte/macrophage lineage are described. Pb exerts a dose-dependent alteration in differentiation of monocyte/macrophage cells that retain some plasticity in development. Pb induces a bifurcation in differentiation of monocyte/macrophage cells, resulting in inhibition of osteoclastogenesis and induction of dendritic cells (DC). This phenomenon was demonstrated in RAW 264.7 murine monocyte/macrophage cell line and was consistent with response in rat bone-marrow derived macrophage (Sprague-Dawley). Pb primarily produced this response through induction of GM-CSF production and inhibition of p38/MAPK activity. Long-term exposure to physiologically relevant concentrations of Pb has the potential to modulate the immune system through altering the cell-lineage commitment of monocyte/macrophage lineage cells in a dose-dependent manner. Thus, Pb may function as an immunomodulator.