Non-coplanar PCBs induce calcium mobilization in bottlenose dolphin and beluga whale, but not in mouse leukocytes.
Polychlorinated biphenyls (PCBs) have been demonstrated to modulate marine mammal immune functions; however, the underlying mechanisms involved are poorly understood. Cytosolic calcium (Ca2+) is an important second messenger involved in numerous leukocyte functions. The direct effects of in vitro exposure to PCBs on Ca2+ mobilization were evaluated in leukocytes isolated from bottlenose dolphins, beluga whales, and B6C3F1 mice. Concentration- and time-response experiments with three non-coplanar PCBs (138, 153, 180), one coplanar PCB (169), and TCDD were tested. Exposure to the three non-coplanar PCBs significantly increased cytosolic Ca2+ in dolphin neutrophils, while PCB 180 significantly increased cytosolic Ca2+ in beluga neutrophils. Two non-coplanar PCBs (138 and 153) significantly increased Ca2+ in beluga monocytes, yet the response was delayed compared to that in neutrophils. Neither PCBs nor TCDD increased cytosolic Ca2+ in mouse neutrophils or monocytes. In experiments with Ca2+-free medium, only PCB 153 increased cytosolic Ca2+ in dolphin neutrophils, though the increase was less than that observed with Ca2+-supplemented medium, suggesting that extracellular Ca2+ was the predominant source for the rise in cytosolic Ca2+. Furthermore, in cells incubated with Ca2+-free medium, a significant increase in cytosolic Ca2+ was induced by thapsigargin following PCB exposure, indicating that intracellular Ca2+ was available, yet not mobilized by the PCBs, and further suggesting that PCBs mobilize extracellular Ca2+. These results demonstrate for the first time the direct effects of non-coplanar PCBs on Ca2+ mobilization in marine mammals, which may be involved in the modulation of phagocytosis previously observed in these species.
Levin
Milton
M
Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, Connecticut 06269, USA. milton.levin@uconn.edu
Morsey
Brenda
B
De Guise
Sylvain
S
D000704:Analysis of Variance; D000818:Animals; D050643:Beluga Whale / Q000276:immunology*; D050681:Bottle-Nosed Dolphin / Q000276:immunology*; D002118:Calcium / Q000097:blood*; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects*; D051379:Mice / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D014874:Water Pollutants, Chemical; D011078:Polychlorinated Biphenyls; D002118:Calcium