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Activated platelets and monocytes generate four hydroxyphosphatidylethanolamines via lipoxygenase
Benjamin H Maskrey1, Alexandra Bermúdez-Fajardo, Alwena H Morgan
1Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff, Wales, United Kingdom.
The Journal of Biological Chemistry
|May 24, 2007
Summary
New research reveals that immune cells generate novel esterified lipids, specifically 15-hydroxyeicosatetraenoic acid (15-HETE) and 12-HETE, bound to phosphatidylethanolamine (PE). These findings expand our understanding of lipoxygenase (LOX) signaling in inflammation.
Area of Science:
- Lipidomics
- Immunology
- Biochemistry
Background:
- 12/15-Lipoxygenase (LOX) has immune-regulatory roles beyond known free acid eicosanoids.
- Activated immune cells may produce additional, uncharacterized LOX-derived lipids.
Purpose of the Study:
- To identify and characterize novel lipids generated by the LOX pathway in activated human immune cells.
- To investigate the formation and nature of these novel LOX metabolites.
Main Methods:
- Lipidomic analysis using precursor scanning electrospray ionization/tandem spectroscopy (MS).
- Identification of lipid species using tandem spectroscopy and MS3.
- Stable isotope labeling with H(18)(2)O to confirm lipid synthesis pathways.
Main Results:
- Human monocytes produced 10-fold more esterified 15-hydroxyeicosatetraenoic acid (15-HETE) than free 15-HETE.
- Identified 15-HETE incorporated into diacyl and plasmalogen phosphatidylethanolamines (PE).
- Human platelets generated analogous PE-esterified 12-HETE, which increased upon stimulation and remained intracellular.
Conclusions:
- Immune cells form PE-esterified HETEs, representing a novel class of LOX metabolites.
- This esterification is specific to the LOX pathway, unlike prostanoid synthesis.
- These novel lipids may play a significant role in LOX-mediated inflammatory signaling.
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