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Updated: Jan 14, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
CD73-enriched extracellular vesicles reduce cyclooxygenase 2 (COX-2)-mediated inflammation in activated macrophages
Md Mostafizur Rahman1, Ravi Shankar Akundi1
1Neuroinflammation Research Lab, Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, India.
Background:
Extracellular ATP (eATP) enhances LPS-mediated activation of cyclooxygenase 2 (COX-2) leading to sustained inflammation. Previous work from our lab has shown that blocking of the purinergic P2 receptors, through which eATP acts, significantly reduced COX-2-mediated inflammation in macrophages and tumor progression in a mouse model of lymphoma. In this report, we test another approach to reduce eATP concentration through increasing the levels of the ectonucleotidase, CD73.
Methods:
Extracellular vesicles (EVs) were isolated from CD73-transfected J774A.1 macrophage cells. CD73-rich EVs were then used to test the effect of eATP on LPS-treated cells.
Results:
J774A.1 cells treated with both LPS and ATP released EVs rich in various pro-inflammatory cytokines and COX-2. Addition of CD73-rich EVs to macrophages treated with both LPS and ATP showed significant reduction in COX-2 expression. This reduction is due to a decrease in the activation of upstream nuclear factor κB (NF-κB) and reduced phosphorylation of cyclin-dependent kinase 9 (CDK9), key proteins involved in COX-2 transcription.
Conclusions:
Our study demonstrated that eATP enhanced LPS-mediated inflammation in macrophages which could be significantly reduced upon addition of CD73-rich EVs. Such engineered EVs can, therefore, be explored therapeutically for their anti-inflammatory properties.
Insights
Extracellular ATP (eATP) promotes inflammation. Engineered extracellular vesicles (EVs) enriched with CD73 reduced eATP-induced inflammation in macrophages by lowering cyclooxygenase 2 (COX-2) expression.
Area of Science:
- Immunology
- Cell Biology
Background:
- Extracellular ATP (eATP) exacerbates LPS-induced inflammation by activating cyclooxygenase 2 (COX-2).
- Previous research indicated that blocking purinergic P2 receptors reduced COX-2 inflammation and lymphoma progression.
Purpose of the Study:
- To investigate reducing eATP levels by increasing CD73 ectonucleotidase activity.
- To assess the therapeutic potential of CD73-enriched extracellular vesicles (EVs) in managing inflammation.
Main Methods:
- Isolated EVs from CD73-transfected J774A.1 macrophage cells.
- Applied CD73-rich EVs to LPS-treated macrophages to evaluate their effect on eATP-induced inflammation.
Main Results:
- LPS and ATP treatment induced EVs containing pro-inflammatory cytokines and COX-2.
- CD73-rich EVs significantly decreased COX-2 expression in treated macrophages.
- Reduced COX-2 expression resulted from decreased NF-κB activation and CDK9 phosphorylation.
Conclusions:
- eATP enhances LPS-mediated inflammation in macrophages.
- CD73-rich EVs effectively reduced this inflammation.
- Engineered EVs show promise as a therapeutic strategy for anti-inflammatory applications.
