ROLE OF ALTERATIONS IN CA2-ASSOCIATED SIGNALING PATHWAYS IN THE IMMUNOTOXICITY OF POLYCYCLIC AROMATIC-HYDROCARBONS()

Polycyclic aromatic hydrocarbons (PAHs) are an important class of envi ronmental pollutants that are known to be carcinogenic and immunotoxic . The effects of PAHs on the immune system of various animals and mode ls have been studied for at least 30 yr. Despite these efforts, the me chanism or mechanisms by which PAHs exert their effects on the immune system are still largely unknown. During recent years, the molecular e vents associated with lymphocyte activation and receptor-mediated sign aling have become increasingly clear. Substantial progress has been ma de in understanding the molecular and cellular bases for toxicant-indu ced immune cell injury. Understanding mechanisms of drug or chemical e ffects on the immune system is an important area of research in the fi eld of immunotoxicology, and indeed in all fields of toxicology. Mecha nistic toxicology plays an important role in risk assessment and extra polation of potential human health effects. In this review, we have su mmarized recent evidence that has examined the effects of PAHs on the immune system of animals and humans. In particular, we have focused on the effects of PAHs on cell signaling in lymphoid cells and have exam ined the hypothesis that PAHs alter lymphocyte activation via calcium- dependent mechanisms. Previously published reports are discussed, and new data obtained with murine B cells and cell lines are presented dem onstrating the relationship between alterations in intracellular calci um and immune dysregulation. These data demonstrate a strong associati on between PAH-induced alterations in B- and T-lymphocyte activation a nd changes in calcium homeostasis.