AUTHOR=Kawecka Ada , Stawarska Klaudia , Romanowska-Kocejko Marzena , Żarczyńska-Buchowiecka Marta , Jędrzejewska Agata , Braczko Alicja , Deptuła Milena , Zawrzykraj Małgorzata , Król Oliwia , Frańczak Marika , Harasim Gabriela , Pikuła Michał , Hellmann Marcin , Kutryb-Zając Barbara 

TITLE=Adenosine deaminase mediates endothelial inflammation via an ADA1-CD26 interaction in post-COVID 

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1578973

DOI=10.3389/fphar.2025.1578973

ISSN=1663-9812

ABSTRACT=IntroductionAdenosine deaminase (ADA) isoenzymes play a role in microvascular dysfunction following SARS-CoV-2 infection. This study analyzes the mechanisms behind ADA1-dependent endothelial inflammation in post-COVID-19 syndrome. We investigated whether immune cells from post-COVID patients could contribute to the increased total ADA activity. Additionally, we examined ADA’s enzymatic and extra-enzymatic activities in human primary lung microvascular endothelial cells (HULECs) stimulated with post-COVID patients’ serum.Methods and resultsTreatment of HULECs with sera from post-COVID patients resulted in elevated levels of the ADA1 isoenzyme and the ADA1-anchoring protein, CD26. This increase correlated with enhanced adhesion of THP-1 monocytes/macrophages to HULECs. Inhibiting the ADA1-CD26 interaction with glycoprotein-120 prevented the rise in cell-surface ADA levels in HULECs and reduced the adhesion of THP-1 cells to the endothelium. A similar effect was observed when HULECs were pre-incubated with the SARS-CoV-2 spike protein, which co-localized with CD26 in activated HULECs.ConclusionsWe propose that ADA1 promotes vascular inflammation in post-COVID-19 syndrome through both canonical and non-canonical mechanisms. On one hand, its increased enzymatic activity can suppress adenosine-dependent pathways. On the other hand, ADA1 may function as an adhesion molecule facilitating interactions between immune cells and the endothelium via ADA1-CD26 complexes.