Adenosine in the Thymus

Köröskényi, Krisztina; Joós, Gergely; Szondy, Zsuzsa

doi:10.3389/fphar.2017.00932

Cited by 6 publications

(6 citation statements)

References 94 publications

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“…It is well known that adenosine acts as an extracellular signaling molecule via activation of G-protein-coupled receptors 8,53 and regulates various biological functions in the thymus 4,[35][36][37][38] , including cAMP-induced thymocyte apoptosis 41,54 . However, we were not able to correlate the reduced thymus cellularity in PEG-ADA-treated mice to the persistent high concentration of Ado.…”

Section: Discussionmentioning

confidence: 99%

“…Ado accumulation does not interfere with thymocyte metabolism. Several studies have highlighted that Ado affects T cell development within the thymus 35 . It has been shown that Ado causes defective TCR signaling 4,36 , inhibits T cell activation and expansion by interfering with the progression of cell mitosis 37,38 and triggers cAMP-induced thymocyte apoptosis through DNA cleavage [39][40][41] .…”

Section: Loss Of Ada Expression Does Not Affect Thymic Stromal Cell F...mentioning

confidence: 99%

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Metabolite and thymocyte development defects in ADA-SCID mice receiving enzyme replacement therapy

Moretti

Giardino

Attenborough

et al. 2021

Sci Rep

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Deficiency of adenosine deaminase (ADA, EC3.5.4.4), a housekeeping enzyme intrinsic to the purine salvage pathway, leads to severe combined immunodeficiency (SCID) both in humans and mice. Lack of ADA results in the intracellular accumulation of toxic metabolites which have effects on T cell development and function. While untreated ADA-SCID is a fatal disorder, there are different therapeutic options available to restore ADA activity and reconstitute a functioning immune system, including enzyme replacement therapy (ERT). Administration of ERT in the form of pegylated bovine ADA (PEG-ADA) has proved a life-saving though non-curative treatment for ADA-SCID patients. However, in many patients treated with PEG-ADA, there is suboptimal immune recovery with low T and B cell numbers. Here, we show reduced thymus cellularity in ADA-SCID mice despite weekly PEG-ADA treatment. This was associated with lack of effective adenosine (Ado) detoxification in the thymus. We also show that thymocyte development in ADA-deficient thymi is arrested at the DN3-to-DN4 stage transition with thymocytes undergoing dATP-induced apoptosis rather than defective TCRβ rearrangement or β-selection. Our studies demonstrate at a detailed level that exogenous once-a-week enzyme replacement does not fully correct intra-thymic metabolic or immunological abnormalities associated with ADA deficiency.

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Section: Discussionmentioning

confidence: 99%

Section: Loss Of Ada Expression Does Not Affect Thymic Stromal Cell F...mentioning

confidence: 99%

Metabolite and thymocyte development defects in ADA-SCID mice receiving enzyme replacement therapy

Moretti

Giardino

Attenborough

et al. 2021

Sci Rep

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“…cAMP (cyclic adenosine monophosphate) и протеинкиназа А. В нейтрофилах cAMP сильно задерживает развитие апоптоза [75], хотя в Т-лимфоцитах [76,77] и клетках лейкемических линий [78,79] cAMP индуцирует этот процесс. Основными cAMP-зависимыми белками являются протеинкиназа А и EPAC (exchange protein activated by cAMP), -фактор активации ГТФазы Rap1.…”

Section: основные типы апоптоза нейтрофиловunclassified

Molecular mechanisms of neutrophil apoptosis (review)

Щепеткин

Буданова²,

Malyshev³

et al. 2018

Nauchno-Prakticheskii Zhurnal «Patogenez»

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В обзоре представлены современные данные о механизмах инициации, регуляции и выполнении процесса апоптоза нейтрофилов с участием «рецепторов смерти», митохондрий, белков семейства Bcl-2, PI3-K (phosphatidylinositol 3-kinase), протеинкиназных каскадов p38 MAPK (mitogen-activated protein kinase), ERK (extracellular signal regulated kinase) и JNK (c-Jun N-terminal kinase), протеинкиназ А, В и С, сAMP, белков теплового шока, NF-kB (nuclear factor-kB), кальпаинов, каспаз и их ингибиторов, активных форм кислорода и других факторов. Предложена гипотетическая модель вовлечения апоптотических процессов в регуляцию дифференцировки и реактивности нейтрофилов. This review presented recent data on initiation, regulation, and execution of neutrophil apoptosis with participation of «death receptors», mitochondria, Bcl-2 family proteins, PI3-K (phosphatidylinositol 3-kinase), p38 MAPK (mitogen-activated protein kinase), ERK (extracellular signal regulated kinase) and JNK (c-Jun N-terminal kinase) cascades, protein kinases A, B and C, сAMP, heat shock proteins, NF-kB (nuclear factor-kB), calpains, caspases and theirs inhibitors, reactive oxygen species, and other factors. A speculative model of the apoptotic processes involvement in the regulation of neutrophil differentiation and reactivity was proposed.

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“…These protective functions of adenosine result in its classi ication as a "retaliatory" or "homeostatic" cellular modulator (Jarvis, 2019) . Adenosine (C10H13N5O4) endogenous purine nucleoside molecule is formed intra-and extracellularly by dephosphorylation of ATP (Kazemzadeh-Narbat et al, 2015), with irmly controlled concentration that regulate its intense and diverse biological abilities (Köröskényi et al, 2017;Palmer and Trevethick, 2009). It induces vasodilation, increases oxygen supply and improves blood low in the heart, skeletal muscle, brain, oral mucosa, gingival, tongue and salivary glands.…”

Section: Introductionmentioning

confidence: 99%

Effects of Adenosine A2A Receptor Agonist on Histopathology of Some Oral Tissues in Rabbits

Al-Mashhadane

2020

ijrps

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Adenosine is a protective regulator that act endogenously to restore equilibrium of cellular energy in response to tissue trauma. It can perform such function of different systems in the body by activation of adenosine receptors. Study the effects of systemic administration of the adenosine on tongue and salivary glands tissues in the rabbit model. Thirty male rabbits of body weight of 1.5 ± 0.25kg were included in the study. In control group (15 animals), one ml of distilled water was injected intraperitoneally while in treatment group (15 animals) were injected by adenosine intraperitoneally at a dose of one mg/ml, All animals were sacrificed after 30 days. Serum samples were separated and used for analysis of adenosine deaminase (ADA)and glutathione(GSH). Tissue samples sections from tongue and salivary glands were stained with hematoxylin-eosin (H&E) and examined under a light microscope for histological changes by a blinded pathologist. Histological sections in treatment group showed congestion of blood vessels and infiltration of inflammatory cells with mild hemorrhage among acini of salivary glands. Increased level of adenosine in the body microenvironment may affect tongue and salivary glands tissues by modulating some processes including inflammation and blood vessels.

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Adenosine in the Thymus

Cited by 6 publications

References 94 publications

Metabolite and thymocyte development defects in ADA-SCID mice receiving enzyme replacement therapy

Metabolite and thymocyte development defects in ADA-SCID mice receiving enzyme replacement therapy

Molecular mechanisms of neutrophil apoptosis (review)

Effects of Adenosine A2A Receptor Agonist on Histopathology of Some Oral Tissues in Rabbits

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