SPECIFIC NON-COPLANAR PCB-MEDIATED MODULATION OF BOTTLENOSE DOLPHIN AND BELUGA WHALE PHAGOCYTOSIS UPON IN VITRO EXPOSURE

Abstract

Contaminant-induced immunosuppression by organochlorines (OC), particularly polychlorinated biphenyls (PCBs), has been suspected as a cofactor in the deaths of thousands of marine mammals. One important innate defense mechanism is phagocytosis, the ability of cells to ingest extracellular macromolecules. The present study was aimed at characterizing the immunomodulatory potential of representative OCs on phagocytosis in bottlenose dolphins and beluga whales. The ability of peripheral blood leukocytes to engulf fluorescent microspheres was evaluated using flow cytometry. The immunomodulatory effects of three non-coplanar PCB congeners, 138, 153, and 180, one coplanar PCB, 169, and 2,3,7,8-TCDD and all possible mixtures (26) were tested upon in vitro exposure. In both species, all mixtures containing at least two non-coplanar PCBs significantly reduced both neutrophil and monocyte phagocytosis, with effects more marked in dolphins than in belugas. Coplanar OCs, on their own or when added to non-coplanar congeners, did not further modulate phagocytosis, suggesting an Ah receptor-independent mechanism. Concentration-response experiments with individual congeners further demonstrated a non-coplanar PCB-induced suppression of phagocytosis, while coplanar congeners produced no consistent effects. Our results suggest simple additive interactions of chemicals in a mixture. However, calculation of toxic equivalency (TEQs) failed to predict the experimentally induced immunomodulatory effects of OCs on dolphin and beluga phagocytosis, confirming the Ah receptor-independent nature of the effects on phagocytosis. Overall, our results suggest that non-AhR mechanisms may explain one facet of immunotoxicity (phagocytosis), something that is not captured using the TEQ approach. This is the first report demonstrating the immunomodulatory effects of OCs on dolphin and beluga phagocytosis, and the first overall demonstration of immunomodulatory effects on phagocytosis mediated specifically by non-coplanar PCBs.

The authors acknowledge the staff at Mystic Aquarium, the New York Aquarium, and the US Navy Marine Mammal Program for providing blood samples. Funding for this work was provided by the NCER/ STAR program of the U.S. Environmental Protection Agency, with initial funding from the University of Connecticut Research Foundation. Although the research described in this article has been funded wholly or in part by the U.S. Environmental Protection Agency through grant R-82836101-0 to Sylvain De Guise, it has not been subjected to the agency's required peer and policy review and therefore does not necessarily reflect the views of the agency and no official endorsement should be inferred.