title: Immunomodulatory effects upon in vitro exposure of California sea lion and southern sea otter peripheral blood leukocytes to domoic acid.
abstract: During red tide bloom events, the marine diatom Pseudo-nitzschia produces the toxin domoic acid (DA), which has been associated with stranding and mortality events involving California sea lions (Zalophus californianus) and southern sea otters (Enhydra lutris). In addition to these well-documented DA-induced neurotoxic events, there is increasing concern that DA may exert chronic effects, such as immunomodulation, which may potentially increase an individual's susceptibility to a number of opportunistic infections following nonlethal exposure. We investigated the effects of DA on innate (phagocytosis and respiratory burst) and adaptive (mitogen-induced lymphocyte proliferation) immune functions with the use of peripheral blood leukocytes collected from healthy California sea lions and southern sea otters upon in vitro exposure to 0 (unexposed control), 0.0001, 0.001, 0.01, 0.1, 1.0, 10, and 100 microM DA. Domoic acid did not significantly modulate phagocytosis or respiratory burst in either species. For California sea lions, DA significantly increased ConA-induced T-lymphocyte proliferation upon exposure to DA concentrations ranging from 0.0001 to 10 microM, resulting in a nonlinear dose-response curve. There was no effect on lymphocyte proliferation at the highest concentration of DA tested. No effects on lymphocyte proliferation were observed in southern sea otters. Importantly, the in vitro DA concentrations affecting T-cell proliferation were within or below the range of DA in serum measured in free-ranging California sea lions following natural exposure, suggesting a risk for immunomodulation in free-ranging animals. Understanding the risk for immunomodulation upon DA exposure will contribute in the health assessment and management of California sea lions and southern sea otters, as well as guide veterinarians and wildlife rehabilitators in caring for and treating afflicted animals.
authors.affiliation: Department of Pathobiology and Veterinary Science, University of Connecticut, 61 North, Eagleville Road, U-3089, Storrs, Connecticut 06269, USA. milton.levin@uconn.edu
authors.forename: Milton
authors.initials: M
authors.lastname: Levin
authors.forename: Dhanashree
authors.initials: D
authors.lastname: Joshi
authors.forename: Andrew
authors.initials: A
authors.lastname: Draghi
authors.forename: Frances M
authors.initials: FM
authors.lastname: Gulland
authors.forename: David
authors.initials: D
authors.lastname: Jessup
authors.forename: Sylvain
authors.initials: S
authors.lastname: De Guise
mesh_terms: D000818:Animals; D000835:Animals, Wild / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D003247:Conservation of Natural Resources; D004305:Dose-Response Relationship, Drug; D005260:Female; D056747:Immunomodulation / Q000187:drug effects*; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000633:toxicity*; D010041:Otters / Q000097:blood* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D016897:Respiratory Burst / Q000187:drug effects; D046070:Sea Lions / Q000097:blood* / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology
chemical_list: D009467:Neuromuscular Depolarizing Agents; C012301:domoic acid; D007608:Kainic Acid