Phosphatidylethanolamine-esterified eicosanoids in the mouse: tissue localization and inflammation-dependent formation in Th-2 disease.

Abstract

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.

• Authors: Alwena H Morgan, Vincent Dioszeghy, Benjamin H Maskrey, Christopher P Thomas, Stephen R Clark, Sara A Mathie, Clare M Lloyd, Hartmut Kühn, Nicholas Topley, Barbara C Coles, Philip R Taylor, Simon A Jones, Valerie B O'Donnell
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 284 Issue 32 Pg. 21185-91 (Aug 07 2009) ISSN: 0021-9258 [Print] United States
• PMID: 19531470 (Publication Type: Journal Article)

Chemical References

• Eicosanoids
• Hydroxyeicosatetraenoic Acids
• Lipids
• Lipopolysaccharides
• Phosphatidylethanolamines
• phosphatidylethanolamine
• 15-hydroxy-5,8,11,13-eicosatetraenoic acid

Topics

• Animals
• Eicosanoids (metabolism)
• Humans
• Hydroxyeicosatetraenoic Acids (chemistry)
• Inflammation
• Lipids (chemistry)
• Lipopolysaccharides (metabolism)
• Macrophages (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Phosphatidylethanolamines (metabolism)
• Staphylococcus epidermidis (metabolism)
• Th2 Cells (metabolism)