Neutrophil Extracellular Traps

Neutrophil Extracellular Traps (NETs) are potentially of interest to us.

This image from a 2020 paper by a Chinese team
(Neutrophil Extracellular Traps: Signaling Properties and Disease Relevance
Tiewei Li, Zhengyan Zhang, Xiaojuan Li, Geng Dong, Min Zhang, Zhe Xu, and Junmei Yang)
gives a feel for what is going on.

Neutrophils are a type of white blood cell; they are part of the immune system. When activated, they throw out fibres of DNA, comprised of histone and cytoplasmic granule proteins. The fibres can capture pathogens, degrade toxins and kill bacteria. And they can provide scaffolding for protein and cell binding and can help in blood clotting.



But, like a lot of the immune system it seems, things can go wrong and there can be collateral damage. Tissues nearby can be damaged due to the proteins carried (as is the case in the picture, with damage to the endothelium) or clotting can happen where it isn't helpful.

It's being suggested that excessive formation of these NETs can lead to a range of diseases (like autoimmune diseases, sepsis, thrombosis and atherosclerosis). And that managing the formation of NETs could prevent or treat quite a number of health conditions.

 

NETs are thought to be formed in three ways:

Vesicle-mediated release - vesicles wrapped with DNA come out of the cell nucleus and travel to the cell membrane where they fuse with the membrane, to release the DNA.

Cell lytic - the cell and the nuclear membrane breaks up, releasing the DNA

Mitochondrial DNA - neutrophils release mitochondrial DNA to form NETs.​

Not all NETs are the same, a 2018 study found that NETs formed as a result of stimulation with LPS (lipopolysaccharide - the component of the membrane of gram-negative bacteria) were much more cytotoxic to endothelial cells than those formed spontaneously. So, the cargo the NET carries matters.

A whole lot of things can trigger NET formation - LPS, bacteria, fungi, protozoa, viruses, toxins, cholesterol, calcium antagonists, TNF-a, hydrogen peroxide.

NADPH, mTOR, PAD4 (mediating histone citrullination), PKA, PKC can all regulate NET formation.

 

There are some interesting paragraphs about autoimmune disease and NETs in the 2020 paper. There have been studies finding neutrophils from people with lupus or rheumatoid arthritis are more likely to produce NETs when stimulated than neutrophils from healthy people. It would be good to see some study of NETs in people with ME/CFS.