Signaling by Environmental Polycyclic Aromatic Hydrocarbons in Human Lymphocytes

During the past decade there has been significant progress made in understanding how environmental agents, drugs, certain chemicals present in the diet, and occupational agents affect the immune system of animals and humans. Polycyclic aromatic hydrocarbons (PAHs) are an important class of environmentally prevalent xenobiotics that exert complex effects on the immune system. These agents, typified by benzo(a)pyrene (BaP), have been shown to alter antigen and mitogen receptor signaling pathways, leading to suppression of humoral and cell-mediated immunity, and at high exposure levels to activation of genes involved in apoptosis in lymphoid cells. Interestingly, at low exposure levels, PAHs may actually augment cell signaling pathways, resulting in immune enhancement or an adjuvant effect. While the biochemical targets and mechanisms responsible for immune modulation are still under investigation, several themes are evolving. PAHs, principally through their cytochrome-P450-derived metabolites, activate oxidative and electrophilic signaling pathways in lymphoid and nonlymphoid cells, including myeloid, epithelial, and other cells. Although PAHs affect signaling pathways in nonlymphoid cells leading to complex interactions between antigen-specific and nonspecific immune and inflammatory responses, this brief review focuses on the mechanisms of signaling by environmentally prevalent PAHs in human lymphocytes. Understanding the mechanisms by which xenobiotics alter adaptive and nonadaptive immune responses may shed light on the etiology of environmental and occupational immune diseases.