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Generation and Function of Non-cell-bound CD73 in Inflammation.
Enja Schneider1, Anne Rissiek1, Riekje Winzer1
1Department of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Frontiers in Immunology
|August 13, 2019
Summary
Non-cell-bound CD73, an enzyme crucial for adenosine production, is generated through shedding and extracellular vesicles. This soluble form expands its anti-inflammatory role at inflammation sites.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Extracellular adenine nucleotides mediate cell communication and immune responses.
- CD39 and CD73 ectonucleotidases generate anti-inflammatory adenosine, but co-expression on T cells is rare.
- CD39 expression increases with T cell activation, while CD73 diminishes.
Purpose of the Study:
- To explore the generation and function of non-cell-bound CD73.
- To resolve the paradox of CD73's limited cell surface expression despite its role in adenosine generation.
- To discuss the physiological significance of soluble CD73 in inflammatory conditions.
Main Methods:
- Review of literature on ectonucleotidases, specifically CD73.
- Investigation of mechanisms for CD73 release from cell membranes (e.g., metalloproteinase cleavage, phospholipase shedding).
- Analysis of CD73 localization in lipid rafts and association with extracellular vesicles (EVs).
Main Results:
- Soluble, enzymatically active CD73 has been reported, with AMPase activity detected in bodily fluids.
- Plausible release mechanisms for CD73 include metalloproteinase cleavage and phospholipase-mediated shedding.
- CD73 is found on extracellular vesicles, particularly in tumor microenvironments, and these vesicles possess immunomodulatory functions.
Conclusions:
- Non-cell-bound CD73, generated via shedding and EVs, broadens the enzyme's reach at inflammation sites.
- Understanding soluble CD73 generation is key to its therapeutic potential in inflammatory diseases.
- This review highlights the physiological role of non-cell-bound CD73 in inflammation.
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