Figure 5.

Proposed mechanisms of vascular inflammation in deficiency of ADA2. In the absence of ADA2 activity, there is a decrease in macrophages M2 and an increase in proinflammatory macrophages M1 that release cytokines such as tumor necrosis factor-α (TNF-α). Adenosine (Ado) cannot be converted to inosine (Ino) and binds to its receptors in neutrophils, leading to neutrophil extracellular trap formation, which induces TNF-α release from M1 macrophages. When ADA2 activity decreases, deoxyadenosine (dAdo) concentration increases. dAdo can enter the cell, and is converted to dIno by ADA1, thereby inhibiting the synthesis of SAM and the transmethylation reactions. The reduction in the activity of DNA methyltransferases (DNAMT) leads to the expression of endogenous retroviral elements that result in increased transcription of IFN-β (interferon β). ENT1: equilibrative nucleoside transporter 1. Parts of the figure were drawn by using pictures from Medical gallery of Blausen Medical [257]. Medical gallery of Blausen Medical is licensed under a Creative Commons Attribution 4.0 Unported License (https://creativecommons.org/licenses/by/4.0/ accessed on 23 May 2023).