PAH‐ and PCB‐induced Alterations of Protein Tyrosine Kinase and Cytokine Gene Transcription in Harbor Seal (Phoca Vitulina) PBMC

Abstract

Mechanisms underlying in vitro immunomodulatory effects of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) were investigated in harbor seal peripheral leukocytes, via real-time PCR. We examined the relative genetic expression of the protein tyrosine kinases (PTKs) Fyn and Itk, which play a critical role in T cell activation, and IL-2, a cytokine of central importance in initiating adaptive immune responses. IL-1, the macrophage-derived pro-inflammatory cytokine of innate immunity, was also included as a measure of macrophage function. Harbor seal PBMC were exposed to the prototypic immunotoxic PAH benzo[a]pyrene (BaP), 3,3',4,4',5,5'-hexachlorobiphenyl (CB-169), a model immunotoxic PCB, or DMSO (vehicle control). Exposure of Con A-stimulated harbor seal PBMC to both BaP and CB-169 produced significantly altered expression in all four targets relative to vehicle controls. The PTKs Fyn and Itk were both up-regulated following exposure to BaP and CB-169. In contrast, transcripts for IL-2 and IL-1 were decreased relative to controls by both treatments. Our findings are consistent with those of previous researchers working with human and rodent systems and support a hypothesis of contaminant-altered lymphocyte function mediated (at least in part) by disruption of T cell receptor (TCR) signaling and cytokine production.

Mercury immune toxicity in harbour seals: links to in vitro toxicity

“…However, large inter-individual variability has previously been observed and cytokine expression in seal PBMCs has been found to vary widely, depending also on the duration of MeHg exposure [ 48 ]. A decrease in PBMC IL-2 expression has also been documented in harbour seals following in vitro exposure to PHA and PCB [ 37 ], raising the possibility of additive effects of MeHg and other organic pollutants.…”

Dynamics of lymphocyte subsets in children living in an area polluted by polychlorinated biphenyls

“…Data indicated that early exposures to environmental toxicants could directly impact the development and function of children's immunity. Many populations in polluted areas (such as Europe and North America) may be at risk of immunotoxicity, which could then manifest as diminished host resistance and increased incidence and severity of infectious diseases (Ross et al, 2004;Neale et al, 2005).…”

Brain transcriptomes of harbor seals demonstrate gene expression patterns of animals undergoing a metabolic disease and a viral infection

“…Previous marine mammal studies have identified pinniped immune responses against PhV-1 using enzyme-linked immunosorbent (ELISA), but this offers minimal information about the disease (Harder et al, 1998). Marine mammal studies have applied targeted gene expression techniques using RT-qPCR to examine immune and endocrine responses to immunotoxins and physiological changes (Neale et al, 2005; Hammond, 2005; Tabuchi et al, 2006). However, ELISA and RT-qPCR target a limited number of host gene expressions; thus they do not represent the global host response.…”