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

Abstract

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.

Quantitative Proteomics of Polarised Macrophages Derived from Induced Pluripotent Stem Cells

“…Interestingly, AMPD2 was found to be enriched in M2 iPSDM ( Figure 8 A,C). AMPD2 is an anti-inflammatory mediator that catalyses formation of IMP from AMP [ 56 ].…”

Comparison of In Silico Signal Sequence-Phospholipid Results with Described In Vitro and In Vivo Protein Translocation Studies Seems to Underscore the Significance of Phospholipids

“…The in silico experiments are based on a combined use of lipid-binding prediction using Heliquest and a Heliquest-based Eisenberg plot approach [32], as well as the use of lipid-peptide interaction predictions using MCPep [33]. This approach has been successfully used and described in the literature [34][35][36][37][38][39][40]. The results as described here show remarkable correlations between, for example, the in vitro results of signal sequence alterations and its subsequent consequences on the overall anionic phospholipid dependence of the process and the in silico results of these alterations in the peptide-lipid interactions.…”