Antigen receptor-mediated activation of extracellular related kinase (ERK) in B lymphocytes of teleost fishes.

In mammalian B lymphocytes, engagement of the B cell antigen receptor (BCR) activates several parallel intracellular signaling pathways which ultimately lead to expression of differentiated functions such as cell proliferation and antibody production or to cellular apoptosis. BCR engagement stimulates the classical mitogen activated protein kinase (MAPK) pathway, also called the extracellular-related kinase (ERK) pathway, resulting in activation of the signature terminal enzyme in the pathway, MAPK (or ERK). BCR signaling also activates the phosphatidyl inositol pathway and its key enzyme protein kinase C (PKC). To investigate the ERK pathway in cells of the teleost immune system, peripheral blood leukocytes from red drum or channel catfish were treated with PKC activators or antibodies which crosslink the BCR. Proteins were identified in both red drum and catfish B cells that resembled mammalian ERKs in molecular weight and in their possessing a distinctive pTEpY dual phosphorylation site. BCR-mediated activation of these presumptive teleost ERKs depended in part (red drum) or in total (catfish) on PKC. To our knowledge this represents the first report of a functional MAPK kinase pathway in teleost fish.

Exposure to mercury alters early activation events in fish leukocytes.

Although fish in natural populations may carry high body burdens of both organic and inorganic mercury, the effects of this divalent metal on such lower vertebrates is poorly understood. In this report, inorganic mercury in the form of mercuric chloride (HgCl2) is shown to produce both high-dose inhibition and low-dose activation of leukocytes in a marine teleost fish, Sciaenops ocellatus. Concentrations of inorganic mercury > or = 10 microM suppressed DNA synthesis and induced rapid influx of radiolabeled calcium, as well as tyrosine phosphorylation of numerous cellular proteins. Lower concentrations (0.1-1 microM) of HgCl2 that activated cell growth also induced a slow sustained rise in intracellular calcium in cells loaded with the calcium indicator dye fura-2, but did not produce detectable tyrosine phosphorylation of leukocyte proteins. These studies support the possibility that subtoxic doses of HgCl2 may inappropriately activate teleost leukocytes, potentially altering the processes that regulate the magnitude and specificity of the fish immune response to environmental pathogens.