scholarly journals Phospholipid Arachidonic Acid Remodeling During Phagocytosis in Mouse Peritoneal Macrophages

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 274
Author(s):  
Luis Gil-de-Gómez ◽  
Patricia Monge ◽  
Juan P. Rodríguez ◽  
Alma M. Astudillo ◽  
María A. Balboa ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Peritoneal Macrophages ◽  
Lipid Mediator ◽  
Membrane Phospholipids ◽  
Lipid Profiling ◽  
Surface Receptors ◽  
Cytosolic Phospholipase ◽  
Mouse Peritoneal Macrophages ◽  
Phospholipid Species ◽  
Potential Use

Macrophages contain large amounts of arachidonic acid (AA), which distributes differentially across membrane phospholipids. This is largely due to the action of coenzyme A-independent transacylase (CoA-IT), which transfers the AA primarily from diacyl choline-containing phospholipids to ethanolamine-containing phospholipids. In this work we have comparatively analyzed glycerophospholipid changes leading to AA mobilization in mouse peritoneal macrophages responding to either zymosan or serum-opsonized zymosan (OpZ). These two phagocytic stimuli promote the cytosolic phospholipase A2-dependent mobilization of AA by activating distinct surface receptors. Application of mass spectrometry-based lipid profiling to identify changes in AA-containing phospholipids during macrophage exposure to both stimuli revealed significant decreases in the levels of all major choline phospholipid molecular species and a major phosphatidylinositol species. Importantly, while no changes in ethanolamine phospholipid species were detected on stimulation with zymosan, significant decreases in these species were observed when OpZ was used. Analyses of CoA-IT-mediated AA remodeling revealed that the process occurred faster in the zymosan-stimulated cells compared with OpZ-stimulated cells. Pharmacological inhibition of CoA-IT strongly blunted AA release in response to zymosan but had only a moderate effect on the OpZ-mediated response. These results suggest a hitherto undescribed receptor-dependent role for CoA-independent AA remodeling reactions in modulating the eicosanoid biosynthetic response of macrophages. Our data help define novel targets within the AA remodeling pathway with potential use to control lipid mediator formation

Action Of Ticlopidine On The Oxygenated Metabolism Of Arachidonic Acid In The Mouse Peritoneal Macrophages

1981 ◽  
Author(s):  
M Rigaud ◽  
H Rabinovitch ◽  
J Durand ◽  
J C Breton ◽  
G Rigaud
Keyword(s):  
Arachidonic Acid ◽  
Mammalian Cells ◽  
Culture Medium ◽  
Eicosatrienoic Acid ◽  
Peritoneal Macrophages ◽  
Membrane Phospholipids ◽  
Glass Capillary ◽  
Drug Concentrations ◽  
High Concentrations ◽  
Mouse Peritoneal Macrophages

When ticlopidine is added to macrophages cultures, in the absence of exogenous arachidonic acid, there is a production of both“prostanoids” and“eicosanoids” in the culture medium. These products have been measured using glass capillary gas chomatography prior to multiple ion mass spectrometry. The quantitative determinations are made 5, 15, 25, 35 and 45 minutes after the drug was added to the macrophages cultures. The three drug concentrations used (10-4M, 5.10-5M and 2.5 10-5M) induce a liberation of 6-keto-PGF1α in the culture medium. As in our system 6-keto-PGF1α seems to be the major metabolite of PGI2, ticlopidine is likely to act by releasing important quantities of PGI2 in macrophages. These results suggest an increase of liberation of the endogenous arachidonic acid from the membrane phospholipids of the macrophages or a lack in the acyltransferase system of the cell membranes. The lipoxygenasic pathway was also studied. When ticlopidine is added to macrophages, two products are liberated: . 12-HETE as measured by single iondetection . and 10-hydroxy-ll-12-epoxy, -5, 8, 14-eicosatrienoic acid which comes from an internal rearrangement of the 12-HPETE. In these results, there is a discrepancy between the fact that ticlopidine increases the concentration of 12-HETE and surely its precursor the 12-HPETE and the fact that the synthesis of PGI2 is not inhibited by these high concentrations of hydroperoxide. To understand this phenomenon we studied the production of hydroperoxide when arachidonic acid is incubated with soybean lipoxygenase. When ticlopidine (10-4M) is added to the reaction mixture (AA + soy lipoxygenase) there is an increase of the initial rate and an extent of the reaction as if the enzyme irreversible deactivation was postponed. Ticlopidine could act by suppressing the classical inhibition of PGI2 synthetase by hydroperoxides, in particular 12-HPETE and 15-HPETE, both produced by mammalian cells.

scholarly journals Acute Nicotine Reduces Brain Arachidonic Acid Signaling in Unanesthetized Rats

2009 ◽  
Vol 29 (3) ◽  
pp. 648-658 ◽  
Author(s):  
Lisa Chang ◽  
Stanley I Rapoport ◽  
Henry N Nguyen ◽  
Dede Greenstein ◽  
Mei Chen ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Brain Regions ◽  
Membrane Phospholipids ◽  
Dose Equivalent ◽  
Central Effects ◽  
Postsynaptic Receptors ◽  
Cytosolic Phospholipase ◽  
Presynaptic Release

Nicotine exerts its central effects by activating pre- and postsynaptic nicotinic acetylcholine receptors (nAChRs). Presynaptic nAChRs modulate the release of many neurotransmitters that bind to postsynaptic receptors. These may be coupled to the activation of cytosolic phospholipase A2 (cPLA2), which hydrolyzes arachidonic acid (AA) from membrane phospholipids. We hypothesized that nicotine would modify brain signaling involving AA by binding to nAChRs. Nicotine (0.1 mg/kg, subcutaneously) or saline was injected 2 or 10 mins before infusing [1-14C]AA in unanesthetized rats. The AA incorporation coefficient k∗ (a marker of the AA signal) was measured in 80 brain regions by quantitative autoradiography. Nicotine, compared to saline, when administrated 2 mins before [1-14C]AA infusion, significantly decreased k∗ for AA in 26 regions, including cerebral cortex, thalamus, and habenula—interpeduncular regions, by 13% to 45%. These decreases could be entirely prevented by pretreatment with mecamylamine (1.0 mg/kg, subcutaneously). When administered 10 mins before [1-14C]AA infusion, nicotine did not alter any value of k∗. In summary, nicotine given to unanesthetized rats rapidly reduces signaling involving AA in brain regions containing nAChRs, likely by modulating the presynaptic release of neurotransmitters. The effect shows rapid desensitization and is produced at a nicotine dose equivalent to smoking one cigarette in humans.

scholarly journals Regulation of prostaglandin synthesis by protein kinase C in mouse peritoneal macrophages

1989 ◽  
Vol 260 (2) ◽  
pp. 471-478 ◽  
Author(s):  
H J Pfannkuche ◽  
V Kaever ◽  
D Gemsa ◽  
K Resch
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Membrane Phospholipids ◽  
Dependent Protein Kinase ◽  
Kinase C ◽  
Dependent Protein ◽  
Dose Dependent ◽  
Mouse Peritoneal Macrophages

Resident mouse peritoneal macrophages synthesized and released prostaglandins (PGs) when challenged with 12-O-tetradecanoylphorbol 13-acetate (TPA) or 1,2-dioctanoyl-sn-glycerol (DiC8). Both stimuli were found to activate Ca2+/phospholipid-dependent protein kinase C (PKC). 1-(5-Isoquinolinesulphonyl)-2-methylpiperazine (‘H-7’) and D-sphingosine, known to inhibit PKC by different mechanisms, were able to decrease the PKC activity of macrophages in a dose-dependent manner. Addition of either PKC inhibitor decreased PG synthesis and also the release of arachidonic acid (AA) from phospholipids induced by TPA or DiC8. Simultaneously TPA or DiC8 also decreased incorporation of free AA into membrane phospholipids of macrophages. AA incorporation could be restored, however, by pretreatment with the PKC inhibitors. Our results demonstrate an involvement of PKC in the regulation of PG synthesis in mouse peritoneal macrophages and provide further evidence that reacylation of released fatty acids may be an important regulatory step.

scholarly journals The localization of phospholipase A2 in the secretory granule

1994 ◽  
Vol 300 (3) ◽  
pp. 619-622 ◽  
Author(s):  
S P Chock ◽  
E A Schmauder-Chock ◽  
E Cordella-Miele ◽  
L Miele ◽  
A B Mukherjee
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Secretory Granule ◽  
Secretory Granules ◽  
Lipid Mediator ◽  
Arachidonic Acid Cascade ◽  
Surface Receptors ◽  
The Matrix ◽  
Immunocytochemical Techniques ◽  
Granule Matrix

A heat-resistant phospholipase A2 has been detected in the secretory granules of the mast cell [Chock, Rhee, Tang and Schmauder-Chock (1991) Eur. J. Biochem. 195, 707-713]. By using ultrastructural immunocytochemical techniques, we have now localized this enzyme to the matrix of the secretory granule. Like the cyclo-oxygenase [Schmauder-Chock and Chock (1989) J. Histochem. Cytochem. 37, 1319-1328], this enzyme also adheres tightly to the ribbon-like granule matrix components. The results from Western-blot analysis suggest that it has a molecular mass of about 14 kDa. The localization of the phospholipase A2, the presence of a phospholipid store with millimolar concentrations of calcium and the localization of the enzymes of the arachidonic acid cascade make the secretory granule a natural site for lipid-mediator synthesis. The packaging of phospholipase A2, together with its substrate and the components of the arachidonic acid cascade, in the secretory granule represents a physical arrangement by which the initiation of the cascade and the release of mediators can be directly linked to the stimulation of cell-surface receptors.

Transformation of arachidonic acid into monohydroxy-eicosatetraenoic acids by mouse peritoneal macrophages

Lipids ◽  
1981 ◽  
Vol 16 (7) ◽  
pp. 518-524 ◽  
Author(s):  
Hélène Rabinovitch ◽  
Jacqueline Durand ◽  
Michel Rigaud ◽  
Francois Mendy ◽  
Jean-Christian Breton
Keyword(s):  
Arachidonic Acid ◽  
Peritoneal Macrophages ◽  
Mouse Peritoneal Macrophages

scholarly journals Regulation of macrophage eicosanoid production by hydroperoxy-and hydroxy-eicosatetraenoic acids

1986 ◽  
Vol 233 (1) ◽  
pp. 199-206 ◽  
Author(s):  
J L Humes ◽  
E E Opas ◽  
M Galavage ◽  
D Soderman ◽  
R J Bonney
Keyword(s):  
Cell Culture ◽  
Arachidonic Acid ◽  
Peritoneal Macrophages ◽  
Lipoxygenase Pathway ◽  
Reversible Inhibitors ◽  
Irreversible Inhibitors ◽  
Intracellular Regulation ◽  
Macrophage Populations ◽  
Mouse Peritoneal Macrophages ◽  
Hydroxyeicosatetraenoic Acids

Resident mouse peritoneal macrophages when exposed to zymosan during the first day of cell culture synthesize and secrete large amounts of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4), the respective products of cyclo-oxygenase- and 5-lipoxygenase-catalysed oxygenations of arachidonic acid. Under these conditions of cell stimulation only small amounts of hydroxyeicosatetraenoic acids (HETEs) are concomitantly produced. However, exogenously added arachidonic acid is metabolized to large amounts of 12- and 15-HETE and only relatively small amounts of PGE2. No LTC4 is formed under these conditions. In contrast, resident mouse peritoneal macrophages in cell culture for 4 days synthesized less PGE2 and LTC4 when exposed to zymosan. However, these macrophage populations continue to synthesize 12-HETE from exogenously added arachidonic acid. Zymosan induced the secretion of a lysosomal enzyme, N-acetyl-beta-glucosaminidase, equally in both 1- and 4-day cultures. Both 12- and 15-hydroperoxyeicosatetraenoic acids (HPETEs), the precursors of 12- and 15-HETE, were found to be irreversible inhibitors of the cyclo-oxygenase pathway and reversible inhibitors of the 5-lipoxygenase pathway in macrophages. 15-HETE were found to be reversible inhibitors of both pathways. Thus the oxidation of arachidonic oxidation of arachidonic acid to both prostaglandins and leukotrienes may be under intracellular regulation by products of 12- and 15-lipoxygenases.

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