What do we know about neutrophil extracellular traps inducers?

Background and objective: Neutrophils are phagocytes that make up the biggestnumber of all kinds of white blood cells and play a central role in the innate immunesystem. Neutrophils fight against pathogens by various mechanisms. One of cytolyticstrategies can lead to extracellular extrusion of the nucleus to form web-like DNAstructures called neutrophil extracellular traps (NETs), which are designed withhistones and cationic granule proteins. The objective of this study was to investigatethe different stimuli inducing NETs formation in previous studies.Search Method: Studies published between ۲۰۰۰ and ۲۰۲۱ that examined theneutrophil extracellular traps inducers were identified through a database search ofPubMed and Cochrane.Findings: NETs formation can be induced by different pathogens, such as bacteria,fungi, protozoa, viruses, and specifically microbial components, lipopolysaccharide(LPS), M۱ protein from Streptococcus pyogenes and the lipophosphoglycans fromLeishmania amazonensis. NETs also can be produced by reactive oxygen species (ROS)such as hydrogen peroxide, antibodies and antigen–antibody complexes, cytokines andchemokines (IL-۸, TNF), microcrystals, and other physiological stimuli. Additionally,traps can be induced by TLR۴-activated platelets. Tumor cells and some other factorssuch as nicotine and some nanoparticles can also activate NETosis. Furthermore,phorbol esters (particularly phorbol-۱۲-myristate-۱۳-acetate, PMA), which mimic theaction of diacylglycerol and activate protein kinase C, as well as calcium (ionomycin, A۲۳۱۸۷) and potassium (nigericin) ionophores are commonly utilized to induceNETosis in in vitro investigations. Several agonists induce either Nox-dependent (suchas PMA, LPS, bacteria) or Nox-independent NET formation (such as A۲۳۱۲۸,ionomycin, uric acid crystals). These molecules induce different types of reactiveoxygen species (ROS) (Nox-ROS and Mitochondrial-ROS) which then they activatetranscriptional firing at promotor regions of many genes specially PAD۴ gene leadingto chromatin decondensation and NETs formation.

کلیدواژه ها:

Neutrophil extracellular traps ، NETosis ، Inducer ، Stimuli