Markers of Monocyte Activation Revealed by Lipidomic Profiling of Arachidonic Acid-Containing Phospholipids

Balgoma, David; Astudillo, Alma M.; Pérez-Chacón, Gema; Montero, Olimpio; Balboa, Marı́a A.; Balsinde, Jesús

doi:10.4049/jimmunol.0902883

Cited by 55 publications

(91 citation statements)

References 72 publications

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“…On the contrary, the levels of AA-containing PE remained fairly constant after the zymosan challenge. This situation is remarkably similar to that previously reported for zymosan-stimulated murine macrophages and RAW264.1 macrophage-like cells (50) and zymosan-stimulated human monocytes (41). It is remarkable that in terms of total mass, the amount of AA lost from PI in control and caveolin-1-deficient cells was very similar (0.67 Ϯ 0.09 and 0.73 Ϯ 0.11 nmol/10 6 cells for control and caveolin-1-deficient cells, respectively; means Ϯ S.E., n ϭ 3).…”

Section: Aa Mobilization and Eicosanoid Production In Caveolin-1-defisupporting

confidence: 78%

“…PC, via CoA-IT. The stimulated entry of AA into PE via CoA-independent transacylation reactions has been demonstrated to occur in human neutrophils (9), human monocytes (41), and murine mast cells (70).…”

Section: Discussionmentioning

confidence: 99%

“…Because of the lability of vinyl ether linkages in acid media, plasmanyl (1-alkyl) and plasmenyl (1-alkЈ1Ј-enyl) glycerophospholipids were distinguished by acidifying the samples before lipid extraction (39). For the identification of acyl chains of AA-containing PC species, ionization was carried out in negative mode with post-column addition of acetic acid at a flow rate of 100 l/h as [M ϩ CH 3 CO 2 ] Ϫ adducts, and acyl chains were identified by MS 3 experiments (40,41).…”

Section: Methodsmentioning

confidence: 99%

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Altered Arachidonate Distribution in Macrophages from Caveolin-1 Null Mice Leading to Reduced Eicosanoid Synthesis

Astudillo

Pérez-Chacón

Meana

et al. 2011

Journal of Biological Chemistry

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Background:We have studied the effect of caveolin-1 deficiency on the mechanisms that regulate free arachidonic acid availability. Results: Macrophages from caveolin-1-deficient mice exhibit elevated fatty acid incorporation and remodeling and a constitutively increased CoA-independent transacylase activity. Conclusion: Macrophages from caveolin-1 null mice show decreased arachidonate mobilization and eicosanoid production upon cell stimulation. Significance: Caveolin-1 may play an important and previously unrecognized role in the eicosanoid biosynthetic response of macrophages.

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Section: Aa Mobilization and Eicosanoid Production In Caveolin-1-defisupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Altered Arachidonate Distribution in Macrophages from Caveolin-1 Null Mice Leading to Reduced Eicosanoid Synthesis

Astudillo

Pérez-Chacón

Meana

et al. 2011

Journal of Biological Chemistry

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“…PE and PI molecular species were identified by multiple reaction monitoring experiments on chromatographic effluent by comparison with previously published data (24,(26)(27)(28)(29)(30)(52)(53)(54). Cutoff parameter was set at m/z 150, and fragmentation amplitude was set at one arbitrary unit.…”

Section: Immunoblotmentioning

confidence: 99%

“…In previous work, we investigated the mechanisms of PLA 2 -mediated phospholipid turnover in monocytes and macrophages responding to a variety of stimuli of innate immunity and inflammation (21)(22)(23)(24)(25)(26)(27)(28)(29)(30). In those studies we took advantage of mass spectrometry-based lipidomic approaches to define, at a molecular species level, the phospholipid substrate specificities of the enzymes involved.…”

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confidence: 99%

Group V Secreted Phospholipase A2 Is Upregulated by IL-4 in Human Macrophages and Mediates Phagocytosis via Hydrolysis of Ethanolamine Phospholipids

Rubio

Rodríguez

Gil-de-Gómez

et al. 2015

The Journal of Immunology

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Studies on the heterogeneity and plasticity of macrophage populations led to the identification of two major polarization states: classically activated macrophages or M1, induced by IFN-γ plus LPS, and alternatively activated macrophages, induced by IL-4. We studied the expression of multiple phospholipase A2 enzymes in human macrophages and the effect that polarization of the cells has on their levels. At least 11 phospholipase A2 genes were found at significant levels in human macrophages, as detected by quantitative PCR. None of these exhibited marked changes after treating the cells with IFN-γ plus LPS. However, macrophage treatment with IL-4 led to strong upregulation of the secreted group V phospholipase A2 (sPLA2-V), both at the mRNA and protein levels. In parallel with increasing sPLA2-V expression levels, IL-4–treated macrophages exhibited increased phagocytosis of yeast-derived zymosan and bacteria, and we show that both events are causally related, because cells deficient in sPLA2-V exhibited decreased phagocytosis, and cells overexpressing the enzyme manifested higher rates of phagocytosis. Mass spectrometry analyses of lipid changes in the IL-4–treated macrophages suggest that ethanolamine lysophospholipid (LPE) is an sPLA2-V–derived product that may be involved in regulating phagocytosis. Cellular levels of LPE are selectively maintained by sPLA2-V. By supplementing sPLA2-V–deficient cells with LPE, phagocytosis of zymosan or bacteria was fully restored in IL-4–treated cells. Collectively, our results show that sPLA2-V is required for efficient phagocytosis by IL-4–treated human macrophages and provide evidence that sPLA2-V–derived LPE is involved in the process.

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Phospholipidomic Profile Variation on THP‐1 Cells Exposed to Skin or Respiratory Sensitizers and Respiratory Irritant

Martins

Maciel

Silva

et al. 2016

Journal Cellular Physiology

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Occupational exposure to low molecular weight reactive chemicals often leads to development of allergic reactions such as allergic contact dermatitis and respiratory allergies. Further insights into the interaction of these chemicals with physiopathological relevant cellular models might provide the foundations for novel non-animal approaches to safety assessment. In this work we used the human THP-1 cell line to determine phospholipidome changes induced by the skin sensitizer 1-fluoro-2,4-dinitrobenzene (DNFB), the respiratory allergen hexamethylene diisocyanate (HDI), and the irritant methyl salicylate (MESA). We detected that these chemicals differently induce lipid peroxidation and modulate THP-1 IL-1β, IL-12B, IL-8, CD86, and HMOX1 transcription. Decreased phosphatidylethanolamine content was detected in cells exposed to MESA, while profound alterations in the relative abundance of cardiolipin species were observed in cells exposed to DNFB. All chemicals tested induced a decrease in the relative abundance of plasmanyl phosphatidylcholine species PC (O-16:0e/18:1) and phosphatidylinositol species PI (34:1), while increasing PI (38:4). An increased abundance of oleic acid was observed in the phospholipids of cells exposed to DNFB while a decreased abundance of palmitic acid was detected in cells treated with MESA or DNFB. We conclude that both specific and common alterations at phospholipidome levels are triggered by the different chemicals, while not allowing a complete distinction between them using a Canonical Analysis of Principal Coordinates (CAP). The common effects observed at phospholipids level with all the chemicals tested might be related to unspecific cell cytotoxic mechanisms that nevertheless may contribute to the elicitation of specific immune responses. J. Cell. Physiol. 231: 2639-2651, 2016. © 2016 Wiley Periodicals, Inc.

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Markers of Monocyte Activation Revealed by Lipidomic Profiling of Arachidonic Acid-Containing Phospholipids

Cited by 55 publications

References 72 publications

Altered Arachidonate Distribution in Macrophages from Caveolin-1 Null Mice Leading to Reduced Eicosanoid Synthesis

Altered Arachidonate Distribution in Macrophages from Caveolin-1 Null Mice Leading to Reduced Eicosanoid Synthesis

Group V Secreted Phospholipase A2 Is Upregulated by IL-4 in Human Macrophages and Mediates Phagocytosis via Hydrolysis of Ethanolamine Phospholipids

Phospholipidomic Profile Variation on THP‐1 Cells Exposed to Skin or Respiratory Sensitizers and Respiratory Irritant

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