Phosphatidylethanolamine-esterified Eicosanoids in the Mouse: TISSUE LOCALIZATION AND INFLAMMATION-DEPENDENT FORMATION IN Th-2 DISEASE

In this study, murine peritoneal macrophages from naïve lavage were found to generate four phospholipids that contain 12-hydroxyeicosatetraenoic acid (12-HETE). They comprise three plasmalogen and one diacyl phosphatidylethanolamines (PEs) (16:0p, 18:1p, 18:0p, and 18:0a at sn-1) and are absent in m...

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Bibliographic Details
Published in:The Journal of biological chemistry 2009-08, Vol.284 (32), p.21185-21191
Main Authors: Morgan, Alwena H, Dioszeghy, Vincent, Maskrey, Benjamin H, Thomas, Christopher P, Clark, Stephen R, Mathie, Sara A, Lloyd, Clare M, Kühn, Hartmut, Topley, Nicholas, Coles, Barbara C, Taylor, Philip R, Jones, Simon A, O'Donnell, Valerie B
Format: Article
Language:English
Subjects:
Animals
Eicosanoids - metabolism
Humans
Hydroxyeicosatetraenoic Acids - chemistry
Inflammation
Lipids - chemistry
Lipids and Lipoproteins: Metabolism, Regulation, and Signaling
Lipopolysaccharides - metabolism
Macrophages - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphatidylethanolamines - metabolism
Staphylococcus epidermidis - metabolism
Th2 Cells - metabolism
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Summary:In this study, murine peritoneal macrophages from naïve lavage were found to generate four phospholipids that contain 12-hydroxyeicosatetraenoic acid (12-HETE). They comprise three plasmalogen and one diacyl phosphatidylethanolamines (PEs) (16:0p, 18:1p, 18:0p, and 18:0a at sn-1) and are absent in macrophages from 12/15-lipoxygenase (12/15-LOX)-deficient mice. They are generated acutely in response to calcium mobilization, are primarily cell-associated, and are detected on the outside of the plasma membrane. Levels of 12-HETE-PEs in naïve lavage are in a similar range to those of free 12-HETE (5.5 ± 0.2 ng or 18.5 ± 1.03 ng/lavage for esterified versus free, respectively). In healthy mice, 12/15-LOX-derived 12-HETE-PEs are found in the peritoneal cavity, peritoneal membrane, lymph node, and intestine, with a similar distribution to 12/15-LOX-derived 12-HETE. In vivo generation of 12-HETE-PEs occurs in a Th2-dependent model of murine lung inflammation associated with interleukin-4/interleukin-13 expression. In contrast, in Toll receptor-dependent peritonitis mediated either by live bacteria or bacterial products, 12-HETE-PEs are rapidly cleared during the acute phase then reappear during resolution. The human homolog, 18:0a/15-HETE-PE inhibited human monocyte generation of cytokines in response to lipopolysaccharide. In summary, a new family of lipid mediators generated by murine macrophages during Th2 inflammation are identified and structurally characterized. The studies suggest a new paradigm for lipids generated by 12/15-LOX in inflammation involving formation of esterified eicosanoids.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109.021634