Persistent organic contaminants and contaminant-induced immune and health alterations in the harbor seal, Phoca vitulina.

摘要

Population declines related to viral outbreaks in marine mammals have been associated with polluted waters and high tissue concentrations of persistent, lipophilic contaminants. These observations suggest a contributing role of contaminant-induced alterations leading to decreased host resistance. This hypothesis was investigated in a model species, the harbor seal (HS; Phoca vitulina). In Chapter One, concentrations of PCBs and DDE in whole blood were determined for HS from central California and Bristol Bay, Alaska (reference population). Organochlorines were considerably greater in California HS, and site [PCBs: San Francisco Bay (SFB) > Monterey Bay (MB); DDE: MB > SFB], age class (pups > adults, subadults), and season (summer peak) were significant correlates. In Alaska samples, organochlorine levels were related to sex and age (increasing with age in males, decreasing with age in females). In Chapter Two, PCBs, DDE, and PBDEs in HS from the heavily-contaminated SFB were associated with hematological parameters reflecting seal health. A positive association between leukocyte counts and organohalogen levels, and an inverse relationship between red blood cell count and PBDEs, were observed, indicating the possibility of increased rates of infection and anemia in seals with higher contaminant levels. In Chapter Three, effects of the prototypic PAH, benzo[a]pyrene, and two PCBs, on the T-cell proliferative response to mitogen in HS lymphocytes were assessed in vitro. Benzo[a]pyrene (10 muM) significantly reduced lymphoproliferation; exposures to PCBs and lower concentrations of benzo[a]pyrene produced similar (but nonsignificant) results. In Chapter Four, potential targets of immunomodulatory compounds were characterized via sequencing of HS cDNA encoding protein kinases---molecules responsible for signal transduction and lymphocyte activation. HS kinases (FYN, LYN, ITK, SYK, MAPKK3) showed great homology with human and rodent orthologs, providing a new molecular tool for gene expression studies. This study illuminated factors of contaminant levels in free-ranging HS. In vitro results indicated that extensive accumulation of lipophilic contaminants by top-trophic-level marine mammals could alter T cell activation in vivo and impair cell-mediated immunity. Hematological correlates of contaminant loads in HS of SFB may serve as sentinel responses. Taken together, these results support the hypothesis of contaminant-induced alteration of marine mammal immunity and health.