In vivo evidence for extracellular DNA trap formation

Abstract

Extracellular DNA trap formation is a cellular function of neutrophils, eosinophils, and basophils that facilitates the immobilization and killing of invading microorganisms in the extracellular milieu. To form extracellular traps, granulocytes release a scaffold consisting of mitochondrial DNA in association with granule proteins. As we understand more about the molecular mechanism for the formation of extracellular DNA traps, the in vivo function of this phenomenon under pathological conditions remains an enigma. In this article, we critically review the literature to summarize the evidence for extracellular DNA trap formation under in vivo conditions. Extracellular DNA traps have not only been detected in infectious diseases but also in chronic inflammatory diseases, as well as in cancer. While on the one hand, extracellular DNA traps clearly exhibit an important function in host defense, it appears that they can also contribute to the maintenance of inflammation and metastasis, suggesting that they may represent an interesting drug target for such pathological conditions. Facts •The demonstration of extracellular DNA traps in vivo requires sections of affected tissues, which are to be investigated with special staining techniques. These structures are seen in multiple inflammatory and cancer diseases.Is there a simple biomarker that reflects extracellular DNA trap formation?• What is the contribution of extracellular microbe killing compared to intracellular killing following phagocytosis?• The mechanism of DNA trap formation is unknown.

NETosis: Molecular Mechanisms, Role in Physiology and Pathology

“…Along with the suicidal NETosis described above, there are also mechanisms of DNA release, when neutrophils retain their viability and natural effector functions (for a review, see [ 6 ]). The term “vital NETosis” was used to describe these processes.…”

“…In particular, structures similar to NETs were found in the contents of the appendix [ 2 ]. Later, NETs were found in numerous organs and tissues [ 6 ], however, the question of its protective effect remains open. NETosis is observed in foci of infections and, apparently, slows down the spread of pathogens.…”

The Release Kinetics of Eosinophil Peroxidase and Mitochondrial DNA Is Different in Association with Eosinophil Extracellular Trap Formation

“…Localized activities of toxic granule proteins associated with mtDNA scaffold result in an efficient antimicrobial defense and limited damage to surrounding host tissues [ 15 ]. As part of the innate immune response, EETs are capable of capturing and killing bacteria [ 16 , 17 , 18 , 19 ]. Similar extracellular trap formation can be formed by other cells, e.g., neutrophils [ 20 ], basophils [ 21 ], mast cells [ 22 ], monocytes [ 23 ] and tissue macrophages [ 24 , 25 ].…”

Is There a Role for Basophils in Cancer?

“…Extracellular traps (ETs) are DNA structures released by activated immune cells, including neutrophils, eosinophils, mast cells, macrophages, and basophils (116,117,(152)(153)(154)(155). ETs released by these cells are draped with proteins from primary granules (e.g., myeloperoxidase and elastase) (156), secondary granules (e.g., lactoferrin and pentraxin 3) (156,157), and tertiary granules (e.g., matrix metalloproteinase 9) (156).…”