Immunotoxicity pathway and mechanism of benzo[a]pyrene on hemocytes of Chlamys farreri in vitro

Benzo[a]pyrene (B[a]P), a typical PAHs widely existing in the marine environment, has been extensively studied for its immunotoxicity due to its persistence and high toxicity. Nevertheless, the immunotoxicity mechanism remain incompletely understood. In this study, isolated hemocytes of Chlamys farreri were exposed at three concentrations of B[a]P (5, 10 and 15 mu g/mL), and the effects of B[a]P on detoxification metabolism, signal transduction, humoral immune factors, exocytosis and phagocytosis relevant proteins and immune function at 0, 6, 12, 24 h were studied. Results illustrated the AhR, ARNT and CYP1A1 were significantly induced by B[a]P at 12 h. Additionally, the content of B[a]P metabolite BPDE increased in a dose-dependent manner with pollutants. Under B[a]P stimulation, the expressions of PTK (Src, Fyn) and PLC-Ca2+-PKC pathway gene increased significantly, while the transcription level of AC-cAMP-PKA pathway gene decreased remarkably. Additionally, the expressions of nuclear transcription factors (CREB, NF-kappa B), complement system genes and C-type lectin genes up regulated obviously. The gene expressions of phagocytosis and exocytosis related proteins were also notably affected. 5 mu g/mL B[a]P could promote phagocytosis in a transitory time, but with the increase of exposure time and concentration of B[a]P, the phagocytosis, antibacterial and bacteriolytic activities gradually decreased. These results indicated that similar to vertebrates, BPDE, the metabolite of B[a]P, mediated downstream signal transduction via PTK in bivalves. The declined of the immune defense ability of hemocytes might be closely related to the inhibition of AC-cAMP-PKA pathway and the imbalance of intracellular Ca2+ pathway. In addition, the results manifested that complement and lectin systems play a significant role in regulating immune response. In this study, the direct relationship between detoxification metabolism and immune signal transduction in bivalves under B[a]P stress was demonstrated for the first time, which provided important information for the potential molecular mechanism of B[a]P-induced immune system disorder in bivalves.

Automated summary

This study investigated the effects of Benzo[a]pyrene (B[a]P) on the immune function of Chlamys farreri hemocytes and found that B[a]P caused changes in both detoxification metabolism and immune signal transduction. Additionally, the metabolite of B[a]P, BPDE, mediated signal transduction through the protein tyrosine kinase pathway in bivalves. The study also demonstrated the significant role of the complement and lectin systems in regulating immune response.