Metabolism of 5-hydroxyicosatetraenoate by human neutrophils: production of a novel omega-oxidized derivative.

O’Flaherty, Joseph T.; Wykle, Robert L.; Redman, J F; Samuel, Michael P.; Thomas, Meirion

doi:10.4049/jimmunol.137.10.3277

Cited by 34 publications

(1 citation statement)

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“…However, the major pathway for 5-Oxo-ETE metabolism in human neutrophils is the process of ωoxidation by LTB 4 20-hydroxylase. This pathway contributes to the formation of 5-Oxo-20-HETE [31,32]. In murine macrophages, 5-Oxo-ETE is also metabolized by ω-oxidation.…”

Section: Metabolism Of 5-oxo-etementioning

confidence: 99%

Biological Roles of 5-Oxo-6,8,11,14-Eicosatetraenoic Acid and the OXE Receptor in Allergic Diseases: Collegium Internationale Allergologicum Update 2024

Lin,

Dai,

Wei

et al. 2024

Int Arch Allergy Immunol

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Background: 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-Oxo-ETE) is a metabolite of arachidonic acid shown to promote biological activities in different cell types. Summary: 5-Oxo-ETE is synthesized from the 5-lipoxygenase product 5S-HETE (5S-hydroxy-6,8,11,14-eicosatetraenoic acid) in the presence of the nicotinamide adenine dinucleotide phosphate (NADP)+-dependent enzyme 5-hydroxyeicosanoid dehydrogenase (5-HEDH). Under some conditions that promote oxidation of NADPH to NADP+, such as the respiratory burst in phagocytic cells, eosinophils, and neutrophils, oxidative stress in monocytes and dendritic cells, and cell death, 5-Oxo-ETE synthesis can be dramatically increased. In addition, 5-Oxo-ETE can also be formed in the absence of 5-lipoxygenase in cells through transcellular biosynthesis by inflammatory cell-derived 5S-HETE. This compound performs its biological activities by the highly selective Gi/o-coupled OXE receptor, which is highly expressed on eosinophils, neutrophils, basophils, and monocytes. As such, 5-Oxo-ETE is a potent chemoattractant for these inflammatory cells, especially for eosinophils. Key Messages: Although the pathophysiological role of 5-Oxo-ETE is not clearly understood, 5-Oxo-ETE may be a significant mediator in allergic diseases, such as allergic asthma, allergic rhinitis, and atopic dermatitis. And targeting the OXE receptor may be a novel therapy for this kind of inflammatory condition. Nowadays, selective OXE receptor antagonists are currently under investigation and could become potential therapeutic agents in allergy.

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Section: Metabolism Of 5-oxo-etementioning

confidence: 99%

Biological Roles of 5-Oxo-6,8,11,14-Eicosatetraenoic Acid and the OXE Receptor in Allergic Diseases: Collegium Internationale Allergologicum Update 2024

Lin,

Dai,

Wei

et al. 2024

Int Arch Allergy Immunol

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Synthesis of 5-oxo-6,8, 11, 14-eicosatetraenoic acid by human monocytes and lymphocytes

Zhang

Styhler

Powell

1996

Journal of Leukocyte Biology

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We recently demonstrated that the arachidonate metabolite 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) is converted by a highly specific dehydrogenase in human neutrophils to 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), which is a potent stimulator of these cells. The objective of this study was to determine whether 5-oxo-ETE is also formed by monocytes and lymphocytes. Human monocytes (74 +/- 2% pure) and lymphocytes (86 +/- 1% pure) were prepared by successive centrifugations of leukocytes over Ficoll-Paque and Percoll. Both cell types converted 5-HETE to a single major product, which was identified as 5-oxo-ETE. The formation of 5-oxo-ETE was stimulated about twofold by phorbol myristate acetate (PMA; 30 nM). Dehydrogenase activity in monocyte fractions did not appear to be due to platelet contamination, since depletion of platelets did not reduce enzyme activity. The dehydrogenase was localized in membrane fractions from monocytes and required NADP+ as a cofactor. It was specific for eicosanoids containing a 5S-hydroxyl group followed by a 6-trans double bond. We also investigated the formation of 5-oxo-ETE from endogenous arachidonic acid by monocytes. 5-Oxo-ETE, 5-HETE, and leukotriene B4 (LTB4) were present in comparable amounts after incubation of these cells with A23187. PMA (EC50 approximately 4 nM) stimulated the formation of 5-oxo-ETE and 5-HETE and, to a lesser extent, LTB4. Although monocytes released considerably less 5-HETE and LTB4 than neutrophils, they released comparable amounts of 5-oxo-ETE. Unlike neutrophils, monocytes did not convert any of these substances to detectable amounts of omega-oxidation products. Although lymphocytes were capable of converting 5-HETE to 5-oxo-ETE, they released little or no 5-lipoxygenase products in response to A23187. We conclude that monocytes have a high capacity to synthesize 5-oxo-ETE and that its formation is stimulated by activation of protein kinase C.

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Purification and Characterization of Recombinant Human Neutrophil Leukotriene B4ω-Hydroxylase (Cytochrome P450 4F3)

Kikuta

Kusunose

Sumimoto

et al. 1998

Archives of Biochemistry and Biophysics

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Metabolism of 5-hydroxyicosatetraenoate by human neutrophils: production of a novel omega-oxidized derivative.

Cited by 34 publications

References 0 publications

Biological Roles of 5-Oxo-6,8,11,14-Eicosatetraenoic Acid and the OXE Receptor in Allergic Diseases: Collegium Internationale Allergologicum Update 2024

Biological Roles of 5-Oxo-6,8,11,14-Eicosatetraenoic Acid and the OXE Receptor in Allergic Diseases: Collegium Internationale Allergologicum Update 2024

Synthesis of 5-oxo-6,8, 11, 14-eicosatetraenoic acid by human monocytes and lymphocytes

Purification and Characterization of Recombinant Human Neutrophil Leukotriene B4ω-Hydroxylase (Cytochrome P450 4F3)

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