In neutrophil extracellular trap (NET) formation (NETosis), chromatin decondenses and is expelled extracellularly. Which enzyme is essential for histone citrullination that allows chromatin decondensation during NETosis?

• A Myeloperoxidase (MPO) oxidizing histone tyrosine residues
• B Cathepsin G cleaving histone H1 linker region
• C Neutrophil elastase phosphorylating histone H2A
• D Peptidyl arginine deiminase 4 (PAD4) which citrullinates histones H3 and H4 ✓

Explanation

PAD4 (peptidyl arginine deiminase 4) is the key enzyme mediating NETosis by citrullinating arginine residues on histones H3 and H4. Citrullination reduces the positive charge of histones, weakening their electrostatic interaction with negatively charged DNA and allowing chromatin decondensation. This unwound chromatin, coated with antimicrobial proteins (elastase, MPO, lactoferrin), is then expelled as NETs. MPO contributes to NET killing but does not initiate chromatin decondensation; cathepsin G is a serine protease in granules.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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