Purine Metabolizing Enzymes of Lymphocyte Cell Populations: Correlation between AMP-Deaminase Activity and dATP Accumulation in Murine Lymphocytes

Dornand, Jacques; Clofent, Gisèle; Bonnafous, Jean‐Claude; Favero, Jean; Mani, Jean‐Claude

doi:10.3181/00379727-179-42122

Cited by 2 publications

(2 citation statements)

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“…As stated before, increased levels of eAMPD2 expression might constitute a counter‐regulatory mechanism, promoting the removal of immunostimulatory ATP and providing anti‐inflammatory IMP. AMPD activity has indeed been shown to correlate inversely with ATP levels 135‐137 . Importantly, our RA cohort comprises a diverse population that does not allow for the differential assessment of the impact of disease activity and current immunosuppressive therapy.…”

Section: Discussionmentioning

confidence: 99%

“…AMPD activity has indeed been shown to correlate inversely with ATP levels. [135][136][137] Importantly, our RA cohort comprises a diverse population that does not allow for the differential assessment of the impact of disease activity and current immunosuppressive therapy. Similarly, further experiments will be necessary to determine the relevance of the age-related differences observed in our cohort and ensure that the results were not caused by confounding factors like comorbidities.…”

Section: Discussionmentioning

confidence: 99%

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Surface AMP deaminase 2 as a novel regulator modifying extracellular adenine nucleotide metabolism

et al. 2021

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Adenine nucleotides represent crucial immunomodulators in the extracellular environment. The ectonucleotidases CD39 and CD73 are responsible for the sequential catabolism of ATP to adenosine via AMP, thus promoting an anti‐inflammatory milieu induced by the “adenosine halo”. AMPD2 intracellularly mediates AMP deamination to IMP, thereby both enhancing the degradation of inflammatory ATP and reducing the formation of anti‐inflammatory adenosine. Here, we show that this enzyme is expressed on the surface of human immune cells and its predominance may modify inflammatory states by altering the extracellular milieu. Surface AMPD2 (eAMPD2) expression on monocytes was verified by immunoblot, surface biotinylation, mass spectrometry, and immunofluorescence microscopy. Flow cytometry revealed enhanced monocytic eAMPD2 expression after TLR stimulation. PBMCs from patients with rheumatoid arthritis displayed significantly higher levels of eAMPD2 expression compared with healthy controls. Furthermore, the product of AMPD2—IMP—exerted anti‐inflammatory effects, while the levels of extracellular adenosine were not impaired by an increased eAMPD2 expression. In summary, our study identifies eAMPD2 as a novel regulator of the extracellular ATP‐adenosine balance adding to the immunomodulatory CD39‐CD73 system.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%