Signaling by environmental polycyclic aromatic hydrocarbons in human lymphocytes

During the past decade there has been significant progress made in understa nding how environmental agents, drugs, certain chemicals present in the die t, and occupational agents affect the immune system of animals and humans. Polycyclic aromatic hydrocarbons (PAHs) are an important class of environme ntally prevalent xenobiotics that exert complex effects on the immune syste m. 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 activat ion of genes involved in apoptosis in lymphoid cells. Interestingly, at low exposure levels, PAHs may actually augment cell signaling pathways, result ing in immune enhancement or an adjuvant effect. While the biochemical targ ets and mechanisms responsible for immune modulation are still under invest igation, several themes are evolving. PAHs, principally through their cytoc hrome-P450-derived metabolites, activate oxidative and electrophilic signal ing pathways in lymphoid and nonlymphoid cells, including myeloid, epitheli al, and other cells. Although PAHs affect signaling pathways in non-lymphoi d cells leading to complex interactions between antigen-specific and nonspe cific immune and inflammatory responses, this brief review focuses on the m echanisms of signaling by environmentally prevalent PAHs in human lymphocyt es. Understanding the mechanisms by which xenobiotics alter adaptive and no nadaptive immune responses may shed light on the etiology of environmental and occupational immune diseases. (C) 2000 Academic Press.