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(41-09) Effects of Ortho-Substituted PCBs on Mussel Hemocyte Immune Function. Canesi, Laura*,1, Ciacci, Caterina1, Betti, Michele1, Scarpato, Alfonso1, Gallo, Gabriella2, 1 Istituto di Scienze Fisiologiche, Università di Urbino, Loc. Crocicchia, Urbino (PU), Italy2 DIBISAA, Università di Genova, Viale Benedetto XV, Genova, Italy ABSTRACT- Polychlorinated biphenyls (PCBs) are industrial chemicals which have been released into the environment resulting in widespread and persistent contamination. PCBs exist as 209 different congeners depending on the chlorine substitution on the biphenyl rings. Research into the mechanism of toxicity of PCBs has focused on congeners that can assume a coplanar configuration and that show high affinity for the aryl hydrocarbon (Ah) receptors, with consequent dioxin-like toxic effects. However, it is becoming increasingly clear that, in mammalian cells, certain ortho-chlorine-substituted, non coplanar PCB congeners with low affinity for the Ah receptor can cause neurotoxicity, endocrine disruption, immunosuppression, and alterations of relevant signal transduction systems. Immunosuppression has been mainly associated with alterations of nonspecific immunity, including neutrophil counts and detriment of macrophage phagocytosis. In particular, ortho-substituted, non coplanar congeners can affect neutrophil cell signalling, activating components involved in the transduction of extracellular stimuli, such as tyrosine kinases, PLA2 and Ca2+ fluxes. In this work, the possible effects of different ortho and non-ortho PCB congeners on the immune function of Mytilus hemocytes were evaluated. Moreover, the possibility that PCBs may affect key steps of cell signalling involved in the immune response of mussel haemocytes was investigated. Our data show that acute, short term treatment of hemocytes with orto-substituted PCB congeners differently affect hemocyte lysosomal stability and bacteria-induced lisozyme release. Moreover, the di-ortho substituted TCB P47 strongly inhibited the microbicidal activity of mussel hemocytes. The mechanisms of PCB-induced immunotoxicity involve alterations of tyrosine mediated cell signalling, in particular of MAPK (Mitogen Activated Protein Kinase) activation. Moreover, certain PCB congeners can affect the level of tyrosine phosphorylated STATs (Signal Transducers and Activators of Transcription) thereby influencing gene expression. These results provide the first evidence that ortho-substituted, non coplanar PCBs can exert immunotoxic effects in marine invertebrates probably interfering with tyrosine-mediated cell signalling. Key words: ortho-substituted PCBs, hemocytes, immunotoxicity, cell signalling |
