Leukocyte proliferation mediated by protein kinase C in the marine teleost fish, Sciaenops ocellatus

• Published in: Developmental and comparative immunology Vol. 18; no. 1; pp. 33 - 43
• Main Authors: Burnett, Karen G., Schwarz, Leslie K.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1994; Elsevier Science
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Alkaloids; Animals; Bass - anatomy & histology; Bass - blood; Benzophenanthridines; Biological and medical sciences; Calcimycin - pharmacology; Calcium - blood; Calcium ionophore; Cell Division - drug effects; Cell physiology; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Isoquinolines - pharmacology; Leukocyte proliferation; Leukocytes - cytology; Leukocytes - drug effects; Leukocytes - metabolism; Lymphocytes - cytology; Lymphocytes - drug effects; Marine; Molecular and cellular biology; Monocytes - drug effects; Phenanthridines - pharmacology; Phorbol ester; Phosphatidylinositols - blood; Piperazines - pharmacology; PKC inhibitors; Protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Sciaenops ocellatus; Signal Transduction; Sulfonamides; Tetradecanoylphorbol Acetate - pharmacology; Sciaenops ocellatus; Protein kinase C; Leukocyte proliferation; Calcium ionophore; Phorbol ester; PKC inhibitors; Cell proliferation; Signal transduction; Vertebrata; Calcium; Enzyme; Leukocyte; Pisces; Enzyme inhibitor; Ionophore
• ISSN: 0145-305X; 1879-0089
• DOI: 10.1016/0145-305X(94)90250-X

A major route of signal transduction in mammalian lymphocytes is the phosphatidyl inositol (PI) pathway. As previously demonstrated in the channel catfish, and confirmed in the present work with the red drum, modulators of the PI pathway such as phorbol ester and calcium ionophore acted synergistically to stimulate proliferation of teleost peripheral blood leukocytes (PBL). Red drum PBL also proliferated strongly in response to phorbol ester alone, at doses which were not mitogenic for catfish PBL. Cell depletion studies suggested that macrophage-derived cytokines probably played a role in supporting the mitogenic response to phorbol ester alone. Dose titration studies with a panel of kinase inhibitors suggested that mitogenic and synergistic doses of phorbol ester primarily targeted an enzyme activity similar to protein kinase C (PKC). However, in the same inhibitor studies, the target enzyme was insensitive to staurosporine, suggesting the involvement of an unusual form of PKC. Similary, cell proliferation stimulated by phorbol ester was suppressed, but not eliminated by a calcium channel blocker Verapamil. Thus, while the synergistic action of phorbol ester and calcium ionophore appeared to be mediated by a PI pathway, these studies have suggested that PKC isoforms and membrane ion pumps unique to the lower vertebrates may participate in regulation of the cell cycle.