Differential activation of mitogen-activated protein kinase (MAPK) pathways in teleost leukocytes by environmental metals

Binding antigen triggers multiple signaling pathways that determine whether vertebrate leukocytes will grow, arrest or die. We hypothesize that environmental stressors can alter the balance among these pathways, in particular the mitogen-activated protein kinase pathways (MAPKs). Teleost peripheral blood leukocytes (PBLs) possess at least one MAPK, the extracellular-related kinase pathway (ERK), which correlates with cell growth. Pb, Al, Cr (VI), and U activated ERKs in PBL of red drum, Sciaenops ocellatus, and channel catfish, Ictalurus punctatus, as measured in western blots with anti-activated ERK. Most of the metals that activated ERKs did not suppress cell growth (IC50>100 μM). In contrast, Pb inhibited cell growth (IC50=10 μM). Pb may suppress another MAPK, Jun Kinase, which is associated with mammalian stress responses. These studies suggest that profiles of individual contaminant effects on cell signaling may predict interactive effects of metal mixtures on the vertebrate immune system. (DOE Cooperative Agreement DE-FC02-98CH10902.)