Inhibition of equine mononuclear cell proliferation and leukotriene B4 synthesis by a specific 5-lipoxygenase inhibitor, A-63162

S. C. Olsen From the Departments of Anatomy and Physiology (Olsen, D. Atluru, S. Atluru, Erickson) and Laboratory Medicine (McVey), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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D. Atluru From the Departments of Anatomy and Physiology (Olsen, D. Atluru, S. Atluru, Erickson) and Laboratory Medicine (McVey), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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S. Atluru From the Departments of Anatomy and Physiology (Olsen, D. Atluru, S. Atluru, Erickson) and Laboratory Medicine (McVey), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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D. S. McVey From the Departments of Anatomy and Physiology (Olsen, D. Atluru, S. Atluru, Erickson) and Laboratory Medicine (McVey), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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H. H. Erickson From the Departments of Anatomy and Physiology (Olsen, D. Atluru, S. Atluru, Erickson) and Laboratory Medicine (McVey), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Summary

The lipoxygenase metabolites of arachidonic acid have an important role in lymphocyte activation. We used a specific 5-lipoxygenase inhibitor, A-63162, to examine the role of 5-lipoxygenase (5-lo) in equine blood mononuclear cell (bmc) proliferation and leukotriene B4 (ltb4) synthesis after stimulation with mitogen (phytohemagglutinin, pha) or calcium ionophore (A23187). The A-63162 inhibited pha-induced equine bmc proliferation and, at the same concentration, also inhibited A23187-induced ltb4 synthesis. The presence of exogenous interleukin 2 (il-2) or the cyclooxygenase inhibitor indomethacin, failed to reverse the immunosuppression caused by A-63162. Further, we found that A-63162, at the concentration that inhibited bmc proliferation and ltb4 synthesis, had no effect on bmc viability. The addition of the specific protein kinase C inhibitor, H-7, did not inhibit A23187-induced ltb4 synthesis. Results indicate that 5-lipoxygenase metabolites may have an important role in equine lymphocyte activation and that protein kinase C has no role in regulating ltb4 production after A23187 stimulation.

Summary

The lipoxygenase metabolites of arachidonic acid have an important role in lymphocyte activation. We used a specific 5-lipoxygenase inhibitor, A-63162, to examine the role of 5-lipoxygenase (5-lo) in equine blood mononuclear cell (bmc) proliferation and leukotriene B4 (ltb4) synthesis after stimulation with mitogen (phytohemagglutinin, pha) or calcium ionophore (A23187). The A-63162 inhibited pha-induced equine bmc proliferation and, at the same concentration, also inhibited A23187-induced ltb4 synthesis. The presence of exogenous interleukin 2 (il-2) or the cyclooxygenase inhibitor indomethacin, failed to reverse the immunosuppression caused by A-63162. Further, we found that A-63162, at the concentration that inhibited bmc proliferation and ltb4 synthesis, had no effect on bmc viability. The addition of the specific protein kinase C inhibitor, H-7, did not inhibit A23187-induced ltb4 synthesis. Results indicate that 5-lipoxygenase metabolites may have an important role in equine lymphocyte activation and that protein kinase C has no role in regulating ltb4 production after A23187 stimulation.

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