Inhibition of equine mononuclear cell proliferation and leukotriene B4 synthesis by a specific 5-lipoxygenase inhibitor, A-63162.
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.
Olsen
S C
SC
Department of Anatomy, College of Veterinary Medicine, Kansas State University, Manhattan 66506.
Atluru
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D
Atluru
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McVey
D S
DS
Erickson
H H
HH
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006736:Horses / Q000097:blood*; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D007975:Leukotriene B4 / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D010647:Phenyl Ethers; D010835:Phytohemagglutinins / Q000276:immunology; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors
D000081:Acetamides; D007376:Interleukin-2; D007546:Isoquinolines; D016859:Lipoxygenase Inhibitors; D010647:Phenyl Ethers; D010835:Phytohemagglutinins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; C068663:N-hydroxy-N-(1-(4-(phenylmethoxy)phenyl)ethyl)-acetamide; D007975:Leukotriene B4; D000001:Calcimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D007213:Indomethacin