Lipid Profiling Reveals Glycerophospholipid Remodeling in Zymosan-Stimulated Macrophages

Rouzer, Carol A.; Ivanova, Pavlina T.; Byrne, Mark; Brown, H. Alex; Marnett, Lawrence J.

doi:10.1021/bi0621617

Cited by 55 publications

(54 citation statements)

References 46 publications

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“…This is interesting in the context of the reported fi nding that liberation of arachidonate by cPLA 2 ␣ from membrane phospholipids has been found to be class dependent. This previous study suggests that PCs appear to be the major ultimate source of 20:4 used for eicosanoid biosynthesis during zymosan phagocytosis in murine primary resident peritoneal macrophages, although specifi c 20:4 contain PIs, PGs play minor roles, and other species like PEps can serve as transient sources that are rapidly replenished ( 40,41 ). This may explain why different classes of AA-containing membrane phospholipids show differential expression patterns in our molecular images.…”

Section: Discussionmentioning

confidence: 70%

Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation

Burnum

Cornett

Puolitaival

et al. 2009

Journal of Lipid Research

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Early pregnancy failure often arises due to defects that occur before, during, or immediately after implantation. Even with in vitro fertilization and embryo-transfer techniques, implantation rates remain low in humans, most often as a result of embryos being transferred into nonreceptive uteri ( 1 ). Studying the molecular interactions that regulate implantation will provide a better understanding of these signaling pathways, eventually leading to new approaches to prevent implantation failure.There is evidence that phospholipid metabolism and signaling infl uences early pregnancy events ( 2 ). Phospholipids are vital structural and regulatory components of biological membranes and serve as precursors for many active biomolecules, such as eicosanoids and lysophospholipids ( 3, 4 ). Prostaglandins, one major group of eicosanoid lipid molecules, are produced from arachidonic acid (AA) that is released from membrane phospholipids by phospholipase A 2 . The released AA is acted upon by cyclooxygenases (COXs) to form prostaglandin H 2 , which is then converted to various prostaglandins by specifi c

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Section: Discussionmentioning

confidence: 70%

Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation

Burnum

Cornett

Puolitaival

et al. 2009

Journal of Lipid Research

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150

141

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“…acrophages contain large amounts of arachidonic acid (AA) esterified in membrane glycerophospholipids (1)(2)(3), which makes them a major source of eicosanoids during innate immune reactions. The eicosanoids affect immune regulation by modulating phagocyte cell activation at different points, including differentiation and migration, phagocytic capacity, and cytokine production (4)(5)(6)(7).…”

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confidence: 99%

Cytosolic Group IVA and Calcium-Independent Group VIA Phospholipase A2s Act on Distinct Phospholipid Pools in Zymosan-Stimulated Mouse Peritoneal Macrophages

Gil-de-Gómez

Astudillo

Guijas

et al. 2014

The Journal of Immunology

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Phospholipase A2s generate lipid mediators that constitute an important component of the integrated response of macrophages to stimuli of the innate immune response. Because these cells contain multiple phospholipase A2 forms, the challenge is to elucidate the roles that each of these forms plays in regulating normal cellular processes and in disease pathogenesis. A major issue is to precisely determine the phospholipid substrates that these enzymes use for generating lipid mediators. There is compelling evidence that group IVA cytosolic phospholipase A2 (cPLA2α) targets arachidonic acid–containing phospholipids but the role of the other cytosolic enzyme present in macrophages, the Ca2+-independent group VIA phospholipase A2 (iPLA2β) has not been clearly defined. We applied mass spectrometry–based lipid profiling to study the substrate specificities of these two enzymes during inflammatory activation of macrophages with zymosan. Using selective inhibitors, we find that, contrary to cPLA2α, iPLA2β spares arachidonate-containing phospholipids and hydrolyzes only those that do not contain arachidonate. Analyses of the lysophospholipids generated during activation reveal that one of the major species produced, palmitoyl-glycerophosphocholine, is generated by iPLA2β, with minimal or no involvement of cPLA2α. The other major species produced, stearoyl-glycerophosphocholine, is generated primarily by cPLA2α. Collectively, these findings suggest that cPLA2α and iPLA2β act on different phospholipids during zymosan stimulation of macrophages and that iPLA2β shows a hitherto unrecognized preference for choline phospholipids containing palmitic acid at the sn-1 position that could be exploited for the design of selective inhibitors of this enzyme with therapeutic potential.

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“…exchange of fatty acid residues (2)(3)(4)(5)) is yet another process, which is considered to play an important role in phospholipid homeostasis of mammalian (6), yeast (7), and bacterial (8) membranes. Although the precise role of acyl chain remodeling in membrane phospholipid homeostasis remains unresolved, this process is known to be involved in several important phenomena including (i) arachidonic acid-dependent signaling (9), (ii) generation of cardiolipin species required for proper functioning of enzymes in the inner mitochondrial membrane (10,11), (iii) induced exo-and phagocytosis (12,13), (iv) synthesis of disaturated phospholipid species necessary for functional alveolar surfactant (14), (v) temperature adaptation of poikilothermic animals (15), and (vi) replacement of oxidized fatty acids of phospholipids (16 -18). However, despite its crucial role in several important biological processes, many aspects of phospholipid remodeling remain unresolved.…”

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Electrospray Ionization Mass Spectrometry and Exogenous Heavy Isotope-labeled Lipid Species Provide Detailed Information on Aminophospholipid Acyl Chain Remodeling

Kainu

Hermansson

Somerharju

2008

Journal of Biological Chemistry

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Mammalian cells maintain the phospholipid compositions of their different membranes remarkably constant. Beside de novo synthesis, degradation, and intracellular trafficking, acyl chain remodeling plays an important role in phospholipid homeostasis. However, many key details of this process remain unresolved, largely because of limitations of existing methodologies. Here we describe a novel approach that allows one to study metabolism of individual phospholipid species in unprecedented detail. Forty different phosphatidylethanolamine (PE) or -serine (PS) species with a deuterium-labeled head group were synthesized and introduced to BHK21 or HeLa cells using cyclodextrin-mediated transfer. Their metabolism was then monitored in detail by electrospray ionization mass spectrometry. Atypical PE and PS species were rapidly remodeled at both sn1 and sn2 position, yielding a molecular species profile similar to that the endogenous PE and PS. In contrast, remodeling of exogenous species identical or similar to major endogenous ones was more limited and much slower. Major differences in remodeling pathways and kinetics were observed between species within a class, as well as between corresponding PE and PS species. These data along with those obtained with pharmacological inhibitors strongly suggest that multiple lipid class-specific A-type phospholipases and acyl transferases are involved in aminophospholipid remodeling. In conclusion, the approach described here provides highly detailed information on remodeling of exogenously added (amino)glycerophospholipids and should thus be very helpful when elucidating the proteins and processes maintaining molecular species homeostasis.

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Lipid Profiling Reveals Glycerophospholipid Remodeling in Zymosan-Stimulated Macrophages

Cited by 55 publications

References 46 publications

Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation

Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation

Cytosolic Group IVA and Calcium-Independent Group VIA Phospholipase A2s Act on Distinct Phospholipid Pools in Zymosan-Stimulated Mouse Peritoneal Macrophages

Electrospray Ionization Mass Spectrometry and Exogenous Heavy Isotope-labeled Lipid Species Provide Detailed Information on Aminophospholipid Acyl Chain Remodeling

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