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

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