Allergen‐induced histamine secretion associated with lactate production in mast cells detected by <sup>1</sup>H NMR

Yoshizaki, Kazuo; Arizono, Naoki; Hayano, Takashi; Watari, Hiroshi

doi:10.1002/mrm.1910290604

Cited by 3 publications

(4 citation statements)

References 21 publications

(28 reference statements)

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“…While much is known about mast cell activation, little data concerning the role of glucose metabolism in mast cell responses has been published. Studies from the 1990's suggest that adequate glucose and ATP are required for full mast cell function (12–14), and that lactate is released upon activation by compound 48/80 and polymyxin B in rat mast cells (15). Additionally, studies by Chakravarty showed that glycolytic blockade with 2-deoxyglucose (2-DG), iodoacetate, fluoride and oxamate (OX) suppressed compound 48/80 and antigen-induced histamine release in rat mast cells (16, 17).…”

Section: Introductionmentioning

confidence: 99%

Inhibiting Glycolysis and ATP Production Attenuates IL-33-Mediated Mast Cell Function and Peritonitis

et al. 2018

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Cellular metabolism and energy sensing pathways are closely linked to inflammation, but there is little understanding of how these pathways affect mast cell function. Mast cells are major effectors of allergy and asthma, and can be activated by the alarmin IL-33, which is linked to allergic disease. Therefore, we investigated the metabolic requirements for IL-33-induced mast cell function, to identify targets for controlling inflammation. We found that IL-33 increases glycolysis, glycolytic protein expression, and oxidative phosphorylation (OX PHOS). Inhibiting OX PHOS had little effect on cytokine production, but antagonizing glycolysis with 2-deoxyglucose or oxamate suppressed inflammatory cytokine production in vitro and in vivo. ATP reversed this suppression. Glycolytic blockade suppressed IL-33 signaling, including ERK phosphorylation, NFκB transcription, and ROS production in vitro, and suppressed IL-33-induced neutrophil recruitment in vivo. To test a clinically relevant way to modulate these pathways, we examined the effects of the FDA-approved drug metformin on IL-33 activation. Metformin activates AMPK, which suppresses glycolysis in immune cells. We found that metformin suppressed cytokine production in vitro and in vivo, effects that were reversed by ATP, mimicking the actions of the glycolytic inhibitors we tested. These data suggest that glycolytic ATP production is important for IL-33-induced mast cell activation, and that targeting this pathway may be useful in allergic disease.

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Section: Introductionmentioning

confidence: 99%

Inhibiting Glycolysis and ATP Production Attenuates IL-33-Mediated Mast Cell Function and Peritonitis

et al. 2018

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“…125 Moreover, mast cells isolated from rats infected with the parasite Nippostrongylus brasiliensis as well as rat peritoneal mast cells ex vivo-stimulated with either compound 48/80, polymyxin B, or melittin were reported to both secrete histamine and produce lactate. 126 In accordance with the mainly glycolysis-driven activation of mast cells, inhibiting glycolytic ATP production in bone marrowderived mast cells (BMMCs) in vitro was shown to attenuate IL-33mediated mast cell function while inhibiting OxPhos had little effect on cytokine production. 37 Moreover, inhibition of mast cell glycolysis also inhibited IL-33-induced neutrophil recruitment and cytokine production in vivo.…”

Section: Mast Cellsmentioning

confidence: 95%

“…This reduction of mediator release was suggested to be due to the inhibition of ATP‐dependent Ca 2+ ‐release from intracellular calcium stores 125 . Moreover, mast cells isolated from rats infected with the parasite Nippostrongylus brasiliensis as well as rat peritoneal mast cells ex vivo‐stimulated with either compound 48/80, polymyxin B, or melittin were reported to both secrete histamine and produce lactate 126 …”

Section: Metabolic Changes In Different Types Of Immune Cellsmentioning

confidence: 99%

Immune metabolism in allergies, does it matter?—A review of immune metabolic basics and adaptations associated with the activation of innate immune cells in allergy

Goretzki

Lin

Schülke

2021

Allergy

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Type I allergies are pathological, type 2 inflammatory immune responses against otherwise harmless environmental allergens that arise from complex interactions between different types of immune cells. Activated immune cells undergo extensive changes in phenotype and function to fulfill their effector functions. Hereby, activation, differentiation, proliferation, migration, and mounting of effector responses require metabolic reprogramming. While the metabolic changes associated with activation of dendritic cells, macrophages, and T cells are extensively studied, data about the metabolic phenotypes of the other cell types critically involved in allergic responses (epithelial cells, eosinophils, basophils, mast cells, and ILC2s) are rather limited. This review briefly covers the basics of cellular energy metabolism and its connection to immune cell function. In addition, it summarizes the current state of knowledge in terms of dendritic cell and macrophage metabolism and subsequently focuses on the metabolic changes associated with activation of epithelial cells, eosinophils, basophils, mast cells, as well as ILC2s in allergy. Interestingly, the innate key cell types in allergic inflammation were reported to change their metabolic phenotype during activation, shifting to either glycolysis (epithelial cells, M1 macrophages, DCs, eosinophils, basophils, acutely activated mast cells), oxidative phosphorylation (M2 macrophages, longer term activated mast cells), or fatty acid oxidation (ILC2s). Therefore, immune metabolism is of relevance in allergic diseases and its connection to immune cell effector function needs to be considered to better understand induction and maintenance | INTRODUC TI ONAllergic diseases are an increasing health and economic problem in developed countries with IgE-mediated type I hypersensitivity disorders reported to affect more than 25% of the population. 1,2 Immunologically, onset and maintenance of type I allergies are caused by exaggerated type 2-mediated immune responses, directed against otherwise harmless environmental antigens. The main effector cells involved in establishment and elicitation of allergic reactions are antigen-presenting cells (dendritic cells (DCs) and macrophages), Th2 cells, IgE-producing plasma cells, eosinophils, basophils, mast cells, and innate-like lymphocytes type II cells (ILC2s).Additionally, lipid mediators derived from arachidonic acid such as prostaglandins (PGs, eg, PGD4, PGE2) and leukotrienes (LTs, eg, cysLT1), or the peptide hormone histamine (derived from histidine) are produced by activated immune cells within minutes, act locally through specific receptors expressed on many target cells, and are usually quickly metabolized. 3,4 These molecules are prominently involved in the hallmark features of allergic inflammation by inducing potent and bronchoconstriction/long-lasting bronchospasm, immune cell recruitment, airway inflammation, hyperresponsiveness, and remodeling. [3][4][5] Activated immune cells can undergo extensive phenotypic changes in order ...

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“…In 1965, Chakravarty suggested that rat mast cells had higher glycolytic rates than oxidative ones, and some years later he and others pointed out the importance of glucose metabolism and lactate production for histamine release . However, respiration inhibitors block histamine release, and hence energy is necessary for activation and secretion of histamine .…”

Section: Metabolism Of Cells At the Tumor Microenvironmentmentioning

confidence: 99%

Metabolism within the tumor microenvironment and its implication on cancer progression: An ongoing therapeutic target

Ocaña

Martínez‐Poveda

Quesada

et al. 2018

Medicinal Research Reviews

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Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment (TME).Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the TME and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that TME is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with

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Allergen‐induced histamine secretion associated with lactate production in mast cells detected by ¹H NMR

Cited by 3 publications

References 21 publications

Inhibiting Glycolysis and ATP Production Attenuates IL-33-Mediated Mast Cell Function and Peritonitis

Inhibiting Glycolysis and ATP Production Attenuates IL-33-Mediated Mast Cell Function and Peritonitis

Immune metabolism in allergies, does it matter?—A review of immune metabolic basics and adaptations associated with the activation of innate immune cells in allergy

Metabolism within the tumor microenvironment and its implication on cancer progression: An ongoing therapeutic target

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Allergen‐induced histamine secretion associated with lactate production in mast cells detected by 1H NMR

Cited by 3 publications

References 21 publications

Inhibiting Glycolysis and ATP Production Attenuates IL-33-Mediated Mast Cell Function and Peritonitis

Inhibiting Glycolysis and ATP Production Attenuates IL-33-Mediated Mast Cell Function and Peritonitis

Immune metabolism in allergies, does it matter?—A review of immune metabolic basics and adaptations associated with the activation of innate immune cells in allergy

Metabolism within the tumor microenvironment and its implication on cancer progression: An ongoing therapeutic target

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Allergen‐induced histamine secretion associated with lactate production in mast cells detected by ¹H NMR