NETs (neutrophil extracellular traps) are implicated in pathological thrombosis and tissue damage. What is the cellular mechanism of NET formation?

• A Neutrophil apoptosis releasing nuclear contents passively into the extracellular space
• B Neutrophil degranulation releasing preformed granule contents including elastase and MPO
• C Caspase-3-mediated DNA fragmentation releasing chromatin with attached granule proteins
• D Active NADPH oxidase-dependent ROS generation causing histone citrullination by PAD4, chromatin decondensation, and membrane rupture ✓

Explanation

NET formation (NETosis) requires NADPH oxidase-dependent ROS production activating peptidylarginine deiminase 4 (PAD4), which citrullinates histones H3 and H4, causing chromatin decondensation. The nuclear envelope then breaks down, DNA mixes with granule proteins (elastase, MPO, cathepsin G), and the plasma membrane ruptures releasing the NET scaffold. Vital NETosis (preserving cell viability) occurs through vesicular exocytosis. NETs are implicated in COVID-19 thrombosis, lupus, and ANCA vasculitis pathogenesis.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.