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 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.
Morgan
Alwena H
AH
Department of Medical Biochemistry and Immunology, Tenovus Building, Heath Park, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
Dioszeghy
Vincent
V
Maskrey
Benjamin H
BH
Thomas
Christopher P
CP
Clark
Stephen R
SR
Mathie
Sara A
SA
Lloyd
Clare M
CM
Kühn
Hartmut
H
Topley
Nicholas
N
Coles
Barbara C
BC
Taylor
Philip R
PR
Jones
Simon A
SA
O'Donnell
Valerie B
VB
D000818:Animals; D015777:Eicosanoids / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000737:chemistry*; D007249:Inflammation; D008055:Lipids / Q000737:chemistry; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D013212:Staphylococcus epidermidis / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism*
D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; D008055:Lipids; D008070:Lipopolysaccharides; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid