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I now have all the information needed to answer this question definitively.
Answer: C. Mitochondrial DNA is involved
The correct answer is C - this statement is FALSE about NETs, making it the "except."
Explanation
NETs (Neutrophil Extracellular Traps) are extracellular fibrillar networks that trap and kill microbes. Here is why each option is TRUE or FALSE:
A. Seen in sepsis - TRUE
NETs have been detected in the blood during sepsis. Platelet TLR4 activates NETs to ensnare bacteria in septic blood, and this is a well-documented phenomenon.
- Robbins Pathologic Basis of Disease: "NETs have also been detected in the blood during sepsis."
B. Seen with bacteria - TRUE
NETs are produced in response to infectious pathogens, "mainly bacteria and fungi." Multiple pathogens including bacteria, fungi, viruses, and protozoa induce NET formation.
- Robbins: "They are produced by neutrophils in response to infectious pathogens (mainly bacteria and fungi)..."
C. Mitochondrial DNA is involved - FALSE (the EXCEPT)
NETs are composed of nuclear chromatin (nuclear DNA), not mitochondrial DNA. The process specifically involves nuclear envelope rupture and extrusion of nuclear DNA decorated with granular antimicrobial proteins. NET formation starts with ROS-dependent arginine deaminase activation, leading to chromatin (nuclear) decondensation, followed by rupture of the nuclear envelope and release of chromatin into the extracellular space.
- Robbins: "The extracellular traps consist of a viscous meshwork of nuclear chromatin..."
- Greenfield's Surgery: "NETosis is a process in which neutrophils extrude a lattice of chromatin and histones...the characteristic feature is the presence of neutrophil nuclear DNA in the extracellular space."
D. Release antimicrobial products - TRUE
NETs carry a rich array of microbicidal compounds attached to the chromatin backbone: neutrophil elastase (NE), myeloperoxidase (MPO), cathepsin G, histones H1-H4, proteinase 3, lactoferrin, calprotectin, and antimicrobial peptides (e.g., defensins, LL-37).
- Greenfield's Surgery: "Attached to this DNA backbone is an array of microbicidal agents...NE, cathepsin G, and MPO."
Key Memory Point
NETs = Nuclear DNA + granule proteins. The nuclear chromatin unravels, mixes with cytoplasmic granule contents, and bursts out of the cell. Mitochondrial DNA plays no role in this classical NETosis pathway. (Note: some research describes a "vital NETosis" involving mitochondrial DNA in very specific low-stimulation contexts, but the classical and standard teaching is that NETs are formed from nuclear chromatin.)
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