Cellular Mechanisms of NETosis

Thiam, Hawa Racine; Wong, Siu Ling; Wagner, Denisa D.; Waterman, Clare M.

doi:10.1146/annurev-cellbio-020520-111016

Cited by 286 publications

(305 citation statements)

References 167 publications

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“…During NETosis, PMN undergo morphological changes, which include the disintegration of nuclear and granule membranes and the combination of nuclear, granular, and cytoplasmic components; the final result is the formation of traps made up of DNA and antimicrobial proteins. These extracellular traps allow capturing microbial agents and spermatozoa [ 57 ]. Therefore, further studies should elucidate whether the modifications of the sperm surface due to selection through SLC modify the ability of PMN to trigger NETosis, and determine the impact upon sperm fertilizing ability and endometrial reaction in the jenny.…”

Section: Discussionmentioning

confidence: 99%

Single Layer Centrifugation Improves the Quality of Fresh Donkey Semen and Modifies the Sperm Ability to Interact with Polymorphonuclear Neutrophils

Papas

Catalán

Recuero

et al. 2020

Animals

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This study sought to determine whether single layer centrifugation (SLC) of fresh donkey semen with Equicoll has any impact on sperm quality parameters and on the modulation of endometrial reaction following semen deposition using an in vitro model. Seventeen ejaculates from five jackasses were obtained using an artificial vagina and diluted in a skim-milk extender. Samples were either selected through SLC (Equicoll) or non-treated (control). Two experiments were performed. The first one consisted of incubating selected or non-selected spermatozoa at 38 °C for 180 min. Integrity and lipid disorder of sperm plasma membrane, mitochondrial membrane potential, and intracellular levels of calcium and reactive oxygen species were evaluated at 0, 60, 120, and 180 min. In the second experiment, polymorphonuclear neutrophils (PMN) isolated from jennies blood were mixed with selected and unselected spermatozoa. Interaction between spermatozoa and PMN was evaluated after 0, 60, 120, and 180 min of co-incubation at 38 °C. SLC-selection increased the proportions of spermatozoa with an intact plasma membrane and low lipid disorder, of spermatozoa with high mitochondrial membrane potential and with high calcium levels, and of progressively motile spermatozoa. In addition, selection through SLC augmented the proportion of phagocytosed spermatozoa, which supported the modulating role of seminal plasma proteins on sperm-PMN interaction. In conclusion, SLC of fresh donkey semen increases the proportions of functionally intact and motile spermatozoa, and appears to remove the seminal plasma proteins that inhibit sperm-PMN binding.

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Section: Discussionmentioning

confidence: 99%

Single Layer Centrifugation Improves the Quality of Fresh Donkey Semen and Modifies the Sperm Ability to Interact with Polymorphonuclear Neutrophils

Papas

Catalán

Recuero

et al. 2020

Animals

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“…Based on the recent characterization of new humoral and cellular factors, hemostasis as part of the wound healing process has gained considerable interest as contributor to the body's lifesaving defense mechanism that is embedded in the functional context of innate immunity. Here, self-exRNA and -exDNA were found to be potent cofactors in the initiation of blood coagulation, whereby the neutrophil-derived exDNA/histone scaffolds (designated as NETs) not only serve as potent antiinflammatory gate-keepers that catch and kill microbes but also work as promoters of thrombotic situations in a variety of diseases (Fuchs et al, 2010;Massberg et al, 2010;von Brühl et al, 2012;Döring et al, 2017;Sorvillo et al, 2019;Thålin et al, 2019;Thiam et al, 2020). Since the identification of exRNA as a cofactor for several coagulation and platelet-derived proteins, the exRNA-mediated link between the discussed processes of innate immunity/leukocyte recruitment and the hemostasis system has become apparent.…”

Section: Exrna and Vascular Defense Systems (Contact Phase/coagulatiomentioning

confidence: 99%

Extracellular RNA as a Versatile DAMP and Alarm Signal That Influences Leukocyte Recruitment in Inflammation and Infection

Preissner

Fischer

Deindl³

2020

Front. Cell Dev. Biol.

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Upon vascular injury, tissue damage, ischemia, or microbial infection, intracellular material such as nucleic acids and histones is liberated and comes into contact with the vessel wall and circulating blood cells. Such “Danger-associated molecular patterns” (DAMPs) may thus have an enduring influence on the inflammatory defense process that involves leukocyte recruitment and wound healing reactions. While different species of extracellular RNA (exRNA), including microRNAs and long non-coding RNAs, have been implicated to influence inflammatory processes at different levels, recent in vitro and in vivo work has demonstrated a major impact of ribosomal exRNA as a prominent DAMP on various steps of leukocyte recruitment within the innate immune response. This includes the induction of vascular hyper-permeability and vasogenic edema by exRNA via the activation of the “vascular endothelial growth factor” (VEGF) receptor-2 system, as well as the recruitment of leukocytes to the inflamed endothelium, the M1-type polarization of inflammatory macrophages, or the role of exRNA as a pro-thrombotic cofactor to promote thrombosis. Beyond sterile inflammation, exRNA also augments the docking of bacteria to host cells and the subsequent microbial invasion. Moreover, upon vessel occlusion and ischemia, the shear stress-induced release of exRNA initiates arteriogenesis (i.e., formation of natural vessel bypasses) in a multistep process that resembles leukocyte recruitment. Although exRNA can be counteracted for by natural circulating RNase1, under the conditions mentioned, only the administration of exogenous, thermostable, non-toxic RNase1 provides an effective and safe therapeutic regimen for treating the damaging activities of exRNA. It remains to be investigated whether exRNA may also influence viral infections (including COVID-19), e.g., by supporting the interaction of host cells with viral particles and their subsequent invasion. In fact, as a consequence of the viral infection cycle, massive amounts of exRNA are liberated, which can provoke further tissue damage and enhance virus dissemination. Whether the application of RNase1 in this scenario may help to limit the extent of viral infections like COVID-19 and impact on leukocyte recruitment and emigration steps in immune defense in order to limit the extent of associated cardiovascular diseases remains to be studied.

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“…NETosis was proposed to occur by two different pathways: suicidal NETosis and vital NETosis [26,40,55]. Suicidal NETosis refers to NET formation due to the release of DNA following the death of neutrophils [74]. Vital NETosis is activated by pathogens, bacterial lipopolysaccharide, TLR4-activated platelets, or complement proteins.…”

Section: Netsmentioning

confidence: 99%

“NETs and EETs, a Whole Web of Mess”

et al. 2020

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Neutrophils and eosinophils are granulocytes that have very distinct functions. Neutrophils are first responders to external threats, and they use different mechanisms to control pathogens. Phagocytosis, reactive oxygen species, and neutrophil extracellular traps (NETs) are some of the mechanisms that neutrophils utilize to fight pathogens. Although there is some controversy as to whether NETs are in fact beneficial or detrimental to the host, it mainly depends on the biological context. NETs can contribute to disease pathogenesis in certain types of diseases, while they are also undeniably critical components of the innate immune response. On the contrary, the role of eosinophils during host immune responses remains to be better elucidated. Eosinophils play an important role during helminthic infections and allergic responses. Eosinophils can function as effector cells in viral respiratory infections, gut bacterial infections, and as modulators of immune responses by driving the balance between Th1 and Th2 responses. In particular, eosinophils have biological activities that appear to be quite similar to those of neutrophils. Both possess bactericidal activity, can activate proinflammatory responses, can modulate adaptive immune responses, can form extracellular traps, and can be beneficial or detrimental to the host according to the underlying pathology. In this review we compare these two cell types with a focus on highlighting their numerous similarities related to extracellular traps.

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Cellular Mechanisms of NETosis

Cited by 286 publications

References 167 publications

Single Layer Centrifugation Improves the Quality of Fresh Donkey Semen and Modifies the Sperm Ability to Interact with Polymorphonuclear Neutrophils

Single Layer Centrifugation Improves the Quality of Fresh Donkey Semen and Modifies the Sperm Ability to Interact with Polymorphonuclear Neutrophils

Extracellular RNA as a Versatile DAMP and Alarm Signal That Influences Leukocyte Recruitment in Inflammation and Infection

“NETs and EETs, a Whole Web of Mess”

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