Intracellular concentration of ADA2 is a marker for monocyte differentiation and activation.
10.1007/s11684-024-1110-6
- Author:
Liang DONG
1
;
Bingtai LU
2
;
Wenwen LUO
3
;
Xiaoqiong GU
4
;
Chengxiang WU
5
;
Luca TROTTA
6
;
Mikko SEPPANEN
7
;
Yuxia ZHANG
2
;
Andrey V ZAVIALOV
8
Author Information
1. Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
2. Department of Respiratory Medicine, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Centre, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, 510623, China.
3. International Center for Aging and Cancer (ICAC), Hainan Medical University, Haikou, 571199, China.
4. Guangzhou Women and Children's Medical Center, Guangzhou, 510623, China.
5. Tulane National Primate Research Center, Covington, USA.
6. Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
7. Adult Immunodeficiency Unit, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
8. International Center for Aging and Cancer (ICAC), Hainan Medical University, Haikou, 571199, China. andrey.zavialov@gmail.com.
- Publication Type:Journal Article
- Keywords:
TNF-α;
adenosine deaminase 2 (ADA2);
adenosine deaminase 2 deficiency (DADA2);
macrophage polarization;
monocyte subsets;
pneumonia
- MeSH:
Humans;
Adenosine Deaminase/deficiency*;
Monocytes/cytology*;
Cell Differentiation;
Intercellular Signaling Peptides and Proteins/metabolism*;
Tumor Necrosis Factor-alpha/metabolism*;
Biomarkers/metabolism*;
Macrophages/metabolism*;
Pneumonia/metabolism*
- From:
Frontiers of Medicine
2025;19(2):359-375
- CountryChina
- Language:English
-
Abstract:
Adenosine, a critical molecule regulating cellular function both inside and outside cells, is controlled by two human adenosine deaminases: ADA1 and ADA2. While ADA1 primarily resides in the cytoplasm, ADA2 can be transported to lysosomes within cells or secreted outside the cell. Patients with ADA2 deficiency (DADA2) often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood. Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages. Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages, and its intracellular concentration decreases in cells secreting TNF-α. This suggests that ADA2 may function as a lysosomal adenosine deaminase, regulating TNF-α expression by the cells. Interestingly, pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage (BAL), correlating with elevated pro-inflammatory cytokine levels. Conversely, cord blood has low ADA2 levels, creating a more immunosuppressive environment. Additionally, secreted ADA2 can bind to apoptotic cells, activating immune cells by reducing extracellular adenosine levels. These findings imply that ADA2 release from monocytes during inflammation, triggered by growth factors, may be crucial for cell activation. Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.
