title: Unique effect of arachidonic acid on human neutrophil TNF receptor expression: up-regulation involving protein kinase C, extracellular signal-regulated kinase, and phospholipase A2.
abstract: Arachidonic acid (AA) regulates the function of many cell types, including neutrophils. Although much emphasis has been placed on agonist-induced down-regulation of TNFR, our data show that AA caused a rapid (10-20 min) and dose-dependent (0.5-30 micro M) increase in the surface expression of both classes of TNFR (TNFR1 and TNFR2) on human neutrophils. This increased TNFR expression correlated with an increase in TNF-induced superoxide production. In contrast, the omega3 fatty acids eicosapentaenoic acid, docosahexaenoic acid, and linolenic acid failed to stimulate TNFR expression. Although fMLP and LPS reduced the neutrophil expression of TNFR, when pretreated with AA, fMLP caused an increase in TNFR expression. Consistent with this result was the finding that AA prevented the fMLP-induced receptor release in neutrophil cultures. AA also caused an increase in TNFR expression in matured HL-60 cells (neutrophil-like cells), but a decrease in nonmatured cells and HUVEC. The AA effects were independent of the lipoxygenase and cyclooxygenase pathways, but dependent on protein kinase C, the extracellular signal-regulated kinases 1 and 2, and cytosolic phospholipase A(2). The data demonstrate a unique effect of AA in the inflammatory reaction, through its action on neutrophil TNFR expression, and suggest that AA may regulate the response of neutrophils to TNF by altering its receptor number.
authors.affiliation: Department of Immunopathology, Women's and Children's Hospital, 72 King William Road, North Adelaide, South Australia 5006.
authors.forename: Nahid
authors.initials: N
authors.lastname: Moghaddami
authors.forename: Maurizio
authors.initials: M
authors.lastname: Costabile
authors.forename: Phulwinder K
authors.initials: PK
authors.lastname: Grover
authors.forename: Hubertus P A
authors.initials: HP
authors.lastname: Jersmann
authors.forename: Zhi H
authors.initials: ZH
authors.lastname: Huang
authors.forename: Charles S T
authors.initials: CS
authors.lastname: Hii
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferrante
mesh_terms: D016718:Arachidonic Acid / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology; D015289:Leukotrienes / Q000494:pharmacology; D008054:Lipid Peroxides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008084:Lipoxygenase / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
chemical_list: D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D007527:Isoenzymes; D015289:Leukotrienes; D008054:Lipid Peroxides; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D013481:Superoxides; D016718:Arachidonic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2