Metal-Induced Modulation of Redox Cell-Signaling in the Immune System

Abstract

A large number of metals in the environment enter the human body and exert diverse toxic effects on the immune system-forming cells. These effects may lead to the death of the cells through the mechanism responsible for apoptosis or necrosis, as well as for activation or suppression of immune functions. Activation or suppression of lymphocytes and antigen-presenting cells depends on the kind and concentration of metals in target cells. The metal-generated changes in protein activity, which induce signaling pathways, as well as changes in expression of genes able to regulate the production of such protein molecules as cytokines and their receptors and surface adhesion molecules, predominate in the immunotoxic effects. Insufficient activation or inhibited production of these proteins is manifested by a decreased immunity of the organism (immuno-suppression), whereas their overactivation induces hypersensitivity (allergy, autoimmunization). A growing amount of data confirm that the activation of proteins involved in cellular signaling and the activation of expression of genes regulating the synthesis of proteins participating in the immune response are associated with oxidative metabolism of immune cells. These data also provide evidence that the modulation effect of metals on the immune response proceeds through influencing the mechanisms that control the production of reactive oxygen species.