Substrate Fate in Activated Macrophages: A Comparison between Innate, Classic, and Alternative Activation

Rodríguez-Prados, Juan-Carlos; Través, Paqui G.; Cuenca, Jimena; Rico, Daniel; Aragonés, Julián; Martı́n-Sanz, Paloma; Cascante, Marta; Boscá, Lisardo

doi:10.4049/jimmunol.0901698

Cited by 842 publications

(806 citation statements)

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“…Different cytokines were obtained from PeproTech (London, U.K.). Abs against P2Y 2 , P2Y 4 , P2Y 6 , and P2X 7 receptors were from Alomone Labs (Jerusalem, Israel), anti-GAPDH was from Ambion (Austin, TX), and other Abs were from Santa Cruz Biotechnology (Santa Cruz, CA), Cell Signaling Technology (Danvers, MA), or from the sources described previously (25). Reagents for electrophoresis were obtained from Bio-Rad (Hercules, CA) and Sigma-Aldrich.…”

Section: Methodsmentioning

confidence: 99%

“…Membranes were incubated for 1 h with low-fat milk powder (5%) in PBS (10 mM Tris-HCl [pH 7.4] and 150 mM NaCl) containing 0.1% Tween 20. Blots were incubated overnight at 4˚C with primary Abs against P2Y 2 , P2Y 4 , P2Y 6 , or P2X 7 receptors (1:500 dilution) or the indicated Abs, as described previously (25). The blots were developed by ECL Advance protocol (GE Healthcare), and different exposure times were performed for each blot with a charge-coupled device camera in a luminescent image analyzer (Molecular Imager; Bio-Rad) to ensure the linearity of the band intensities.…”

Section: Western Blottingmentioning

confidence: 99%

“…Although this modulation could play an important role in the anti-inflammatory effects of PGE 2 , less is known about the underlying cross-talk between PGs and P2 signaling. In particular, because macrophage activation can be polarized into proinflammatory ("classically activated" or M1, using microbial stimuli such as LPS, or cytokines such as IFN-g) or anti-inflammatory/proresolution ("alternatively activated" or M2, using IL-4 and/or IL-13 as stimuli) commitment (22)(23)(24)(25), understanding the contributions of P2 receptors to these adaptive responses of macrophages would provide insight into the regulation of the inflammatory signaling. In this work, we analyze the effect of PGE 2 on the main P2 receptors expressed in peritoneal macrophages.…”

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confidence: 99%

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Selective Impairment of P2Y Signaling by Prostaglandin E2 in Macrophages: Implications for Ca2+-Dependent Responses

Través

Pimentel-Santillana

Carrasquero

et al. 2013

The Journal of Immunology

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Extracellular nucleotides have been recognized as important modulators of inflammation via their action on specific pyrimidine receptors (P2). This regulation coexists with the temporal framework of proinflammatory and proresolution mediators released by the cells involved in the inflammatory response, including macrophages. Under proinflammatory conditions, the expression of cyclooxygenase-2 leads to the release of large amounts of PGs, such as PGE2, that exert their effects through EP receptors and other intracellular targets. The effect of these PGs on P2 receptors expressed in murine and human macrophages was investigated. In thioglycollate-elicited and alternatively activated macrophages, PGE2 selectively impairs P2Y but not P2X7 Ca2+ mobilization. This effect is absent in LPS-activated cells and is specific for PGE2 because it cannot be reproduced by other PGs with cyclopentenone structure. The inhibition of P2Y responses by PGE2 involves the activation of nPKCs (PKCε) and PKD that can be abrogated by selective inhibitors or by expression of dominant-negative forms of PKD. The inhibition of P2Y signaling by PGE2 has an impact on the cell migration elicited by P2Y agonists in thioglycollate-elicited and alternatively activated macrophages, which provide new clues to understand the resolution phase of inflammation, when accumulation of PGE2, anti-inflammatory and proresolving mediators occurs.

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Section: Methodsmentioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

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confidence: 99%

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Selective Impairment of P2Y Signaling by Prostaglandin E2 in Macrophages: Implications for Ca2+-Dependent Responses

Través

Pimentel-Santillana

Carrasquero

et al. 2013

The Journal of Immunology

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“…CD36 levels are significantly increased in M2 phenotype mononuclear phagocytes, mediating signals to pathways for M2 polarization through endoplasmic reticulum stress, JNK, and peroxisome proliferatoractivated receptor-γ [157,158]. M1 and M2 macrophages also have distinct metabolic phenotypes [159,160]. While M1 macrophages depend on aerobic glycolysis, fatty acid oxidation is required to sustain M2 macrophages.…”

Section: Inflammation Versus Resolutionmentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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“…Whereas activation of glycolysis favours the proinflammatory response of an immune cell, enhancement of oxidative phosphorylation drives anti-inflammatory actions. Indeed, M2 alternatively activated (anti-inflammatory) macrophages exhibit increased reliance on oxidative phosphorylation over glycolysis for energy production [34]. In addition, lipophagy may attenuate the inflammatory response by promoting the availability of NEFA for oxidative metabolism, a key metabolic pathway that drives an anti-inflammatory trait.…”

Section: The Role Of Autophagy In Adipose Dysfunction and Inflammationmentioning

confidence: 99%

Autophagy in adipose tissue and the beta cell: implications for obesity and diabetes

et al. 2014

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Autophagy is a lysosomal degradation pathway recycling intracellular long-lived proteins and damaged organelles, thereby maintaining cellular homeostasis. In addition to inflammatory processes, autophagy has been implicated in the regulation of adipose tissue and beta cell functions. In obesity and type 2 diabetes autophagic activity is modulated in a tissue-dependent manner. In this review we discuss the regulation of autophagy in adipose tissue and beta cells, exemplifying tissue-specific dysregulation of autophagy and its implications for the pathophysiology of obesity and type 2 diabetes. We will highlight common themes and outstanding gaps in our understanding, which need to be addressed before autophagy could be envisioned as a therapeutic target for the treatment of obesity and diabetes.

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Substrate Fate in Activated Macrophages: A Comparison between Innate, Classic, and Alternative Activation

Abstract: Material

Cited by 842 publications

References 58 publications

Selective Impairment of P2Y Signaling by Prostaglandin E2 in Macrophages: Implications for Ca2+-Dependent Responses

Selective Impairment of P2Y Signaling by Prostaglandin E2 in Macrophages: Implications for Ca2+-Dependent Responses

Microglia and Monocyte-Derived Macrophages in Stroke

Autophagy in adipose tissue and the beta cell: implications for obesity and diabetes

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