title: Presence and regulation of metallothioneins in peripheral blood leukocytes of grey seals.
abstract: Heavy metal residues have been reported at high levels in marine mammals. Although the immunotoxicity of these contaminants has been demonstrated in laboratory models, evaluation of their potential immunotoxicity for human and wildlife species is complicated by variables that modulate the immune response and the immunotoxic effects of xenobiotics under field conditions. Metallothioneins (MT) modulate the bioavaibility of physiological cations and the toxicity of heavy metals. Moreover, these proteins have been demonstrated to modulate immune functions. In the present study, we demonstrated a rapid and sustained increase of transcripts of the two major isoforms of MT (MT-1 and MT-2) in grey seal peripheral blood leukocytes (PBL) exposed in vitro to Zn. This increase in mRNA corresponds to an increase of MT proteins in PBL. However, we demonstrated a high heterogeneity among the three major PBL subpopulations (granulocytes, lymphocytes and monocytes). Monocytes appear to be the most sensitive cells to Zn or Cd exposure. Intracellular MT levels in PBL subpopulations were dependent not only on the duration of exposure and the concentration, but also on the metal species. Cd was more potent than Zn as an inducer of MT in lymphocytes but not in monocytes. Moreover, grey seal peripheral blood lymphocytes are less sensitive to Cd exposure than human lymphocytes. This noninvasive approach helps to better assess the risk of heavy metal exposure by considering the potential role of MT as modulators of immune response.
authors.affiliation: Université de Liège, Océanologie (B6), B-4000 Sart-Tilman, Belgium.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pillet
authors.forename: Michel
authors.initials: M
authors.lastname: Fournier
authors.forename: Lena N
authors.initials: LN
authors.lastname: Measures
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bouquegneau
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Cyr
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002104:Cadmium / Q000494:pharmacology; D002470:Cell Survival; D005434:Flow Cytometry; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008668:Metallothionein / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D046048:Seals, Earless / Q000378:metabolism*; D013268:Stimulation, Chemical; D015032:Zinc / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D002104:Cadmium; D008668:Metallothionein; D015032:Zinc