T6 PM Immune and Endocrine Disruption: Detection and Implication
Tuesday, 15 November 2005: 1:50 PM - 5:30 PM in 324-326

(LEV-1117-664668) Mechanisms involved in the non-coplanar PCB-induced modulation of phagocytosis in marine mammals, humans, and mice.

Levin, M¹, Morsey, B¹, Mori, C¹, Nambiar, P², De Guise, S¹, ¹ University of Connecticut, Storrs, CT, USA² Massachusetts Institute of Technology, Cambridge, MA, USA

ABSTRACT- Contaminant-induced immunosuppression by polychlorinated biphenyls (PCBs) and dioxins has been associated with adverse health effects in marine mammals and humans. Accumulating evidence suggests that non-coplanar, non dioxin-like PCBs, abundant in the tissues of marine mammals and humans and traditionally considered safe, can modulate key leukocyte functions. This study characterized the immunomodulatory potential of mixtures of PCBs and dioxins on leukocyte phagocytosis, an important innate immune response, and compared the relative sensitivity between marine mammals, humans, and mice. Calcium mobilization and biochemical inhibitors were utilized to better characterize the mechanism(s) involved in the modulation of phagocytosis. The effects of three non-coplanar PCBs, one coplanar PCB, as well as 2,3,7,8-TCDD, and all possible mixtures were tested upon in vitro exposure. Results demonstrated (1) all species were not equally sensitive to the effects of PCBs and dioxins on phagocytosis, (2) reduction in phagocytosis was mediated specifically by non-coplanar PCBs in some species, (3) calcium mobilization may have partially mediated the effects in phagocytosis in bottlenose dolphins and beluga whales, (4) G-protein pathways may be involved in the modulation of phagocytosis in bottlenose dolphins, and (5) the effects on phagocytosis could not be accurately predicted by either the currently used toxic equivalency (TEQ) approach or the mouse model. A better understanding of the mechanisms involved in the modulation of phagocytosis by non-coplanar PCBs will help explain differences in susceptibility between different species and the assessment of risks upon exposure to these environmental pollutants.

Key words: PCB, immunotoxicology, phagocytosis, marine mammal