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, thereby promoting an anti-inflammatory milieu induced by the “adenosine halo”. AMPD2 intracellularly mediates AMP deamination to IMP, thus constituting an ambiguous mediator both enhancing the degradation of inflammatory ATP and reducing the formation of protective adenosine. Here, we show that this enzyme is expressed on the cell surface of human immune cells and its predominance may[BF1] modify inflammatory states by altering the extracellular milieu. Surface AMPD2 (eAMPD2) expression on monocytes was verified by immunoblot, mass spectrometry, surface biotinylation, 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 to healthy controls. Furthermore, we observed that extracellular adenosine production was not impaired by an enhanced eAMPD2 expression, while IMP exerted anti-inflammatory effects. In summary, our study identifies eAMPD2 as a novel regulator of the extracellular ATP-adenosine balance adding to the immunomodulatory CD39-CD73 system.

INSTRUMENT(S): Orbitrap Fusion, Q Exactive HF, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Epithelial Cell, Blood

SUBMITTER: Marieluise Kirchner  

LAB HEAD: Philipp Mertins

PROVIDER: PXD022350 | Pride | 2021-11-03

REPOSITORIES: Pride