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Physiological and molecular biomarkers of environmental contaminant-associated immunotoxicity in harbour seals (Phoca vitulina)

Persistent organic pollutants (POPs) have been contaminating the marine environment since the mid 2Oth Century and continue to do so today. The polychlorinated biphenyls (PCBs) are of particular concern, since they are found at high concentrations in marine mammals throughout the Northern Hemisphere, and have been associated with endocrine disruption, reproductive impairment, immunotoxicity, and outbreaks of disease. In this study, samples were obtained from free-ranging harbour seal (Phoca vituilna) pups, which were live-captured in British Columbia, Canada, and Washington State, USA, in order to assess adverse health effects associated with POPs on the immune system of these mammals.
PCBs were the most abundant of the 31 POPs measured in seals, and represented the greatest toxicological concern on the basis of established reference values for laboratory rodents and aquatic wildlife consumers. Seal immune function was assessed using traditional measures of immunotoxicity, including hematology, innate immune function, and adaptive immune function, and related to PCB concentrations while carefully controlling for confounding factors such as age, sex and condition. PCB concentrations negatively correlated to phagocytosis, T lymphocyte proliferative responses, (thymosin-a1-induced) lymphocyte signalling, and lymphocyte counts, and positively associated with the respiratory burst of phagocytes and aryl hydrocarbon receptor (AhR) expression of white blood cells, suggesting chemical-associated immunotoxicity. Parallel experiments, in which harbour seal white blood cells were exposed in vitro to 2,3,7,8-tetrachlorodibenzo-p-dioxin, a potent immunotoxicant, further supported the hypothesis that the observed reduction in immunocompetence in free-ranging seals may be due to an AhR-mediated mechanism of immunotoxicity. Principal component analysis (PCA) of immunological endpoints combined evidence of PCB-associated effects on the immune system as a whole. However, PCA also identified a difference between the immunological profiles of urban seals and those from remote sites, consistent with elevated pathogen abundance due to biological pollution at urban sites.
In a second approach, PCB concentrations were related to concentrations of vitamin A and expression levels of its receptor, the retinoic acid receptor alpha (RARa), which are known to be sensitive to PCB exposure. More contaminated seals were characterised by lower vitamin A concentrations in circulation and in the blubber, as well as higher RARa expression in the blubber. AhR expression and concentrations of thymosin-a1 (a thymic hormone important in lymphocyte development and immune function) did not relate to contaminants when their levels were investigated in seal tissues (blubber, skin), contrasting their sensitivity in white blood cells. These results implied that PCB-associated toxicity may be reflected if a biomarker represents a primary lesion, but might not be extrapolated among tissues in all cases. Secondly, although blubber represents the primary site of PCB storage, it is not necessarily the site of the highest toxicity.
In summary, significant evidence of immunotoxicity and disruption of immune function-related biomarkers has been provided in a healthy group of free-ranging marine mammals which contributes to the weight of evidence that environmental contaminants may render marine mammal populations more vulnerable to disease through immunotoxicity. Immune function measures in free-ranging harbour seal pups exposed to contaminants in vivo, in combination with harbour seal white blood cells in vitro, furthermore suggested that immunotoxicity may take place through an AhR-mediated mechanism of action. An unexpected finding was the evidence of a second, independent, impact on the immune system of seals, consisting of biological pollution. The combination of both chemical and biological pollution, that would imply both diminished immune responses and increased pathogen loads, may represent the largest threat to the health of marine mammals in many parts of the world.

Identiferoai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/2132
Date01 February 2010
CreatorsMos, Elisabeth
ContributorsKoop, Benjamin F., Ross, Peter S.
Source SetsUniversity of Victoria
LanguageEnglish, English
Detected LanguageEnglish
TypeThesis
RightsAvailable to the World Wide Web

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