Adenosine from a biologic source regulates neutrophil extracellular traps (NETs)

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Neutrophil extracellular traps (NETs) are involved in various diseases.
• Endogenous regulation of NETs under basal conditions is poorly understood.
• Extracellular purines like adenosine (ADO) and ATP modulate neutrophil functions.

Purpose of the Study:

• To investigate the effect of adenosine on NET formation.
• To identify the specific adenosine receptors involved in NET regulation.
• To determine the role of mesenchymal stromal cells (MSCs) and CD73 in modulating NETs.

Main Methods:

• Human neutrophils isolated and stimulated to form NETs.
• NET production quantified using SYTOX green fluorescence and HNE-DNA ELISA.
• Adenosine receptor agonists/antagonists and MSC co-cultures were used.

Main Results:

• Adenosine significantly inhibited NET production.
• The adenosine A_2A receptor (A_2A R) agonist CSG21680 mimicked ADO's inhibitory effect.
• A_2A R antagonist ZM241385 blocked ADO's inhibition.
• MSCs reduced NET formation in a CD73-dependent manner.

Conclusions:

• Extracellular purine balance, modulated by stromal cells, may regulate NETosis.
• Adenosine signaling via A_2A R is a key inhibitory pathway for NET formation.
• CD73 on MSCs contributes to the regulation of NETosis in tissue environments.