The role of neutrophil extracellular traps in acute lung injury

Scozzi, Davide; Liao, Fuyi; Krupnick, Alexander S.; Kreisel, Daniel; Gelman, Andrew E.

doi:10.3389/fimmu.2022.953195

Cited by 69 publications

(62 citation statements)

References 178 publications

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“…Previously, we were able to demonstrate systemic neutrophil activation after burn injury 22 . This is in accord with other studies reporting a role for neutrophils and NETs in burn injury 27 ,, ,28 ,critically ill patients 21 , sepsis 29 , and lung injury 30 . Whereas NET formation represents a protective process that captures and sequesters microbes, thereby preventing the spread of infection, a dysregulation of NET formation with increased concentration of extracellular DNA may contribute to the perpetuation of in ammation and severe tissue injury 25,[31][32][33] .…”

Section: Introductionsupporting

confidence: 92%

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Elevation of neutrophil-derived factors in patients after multiple trauma

Lingitz

Wollner

Bauer

et al. 2022

Preprint

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Trauma represents one of the leading causes of death worldwide. Traumatic injuries elicit a dynamic inflammatory response with systemic release of inflammatory cytokines. Disbalance of this response can lead to systemic inflammatory response syndrome or compensatory anti-inflammatory response syndrome. As neutrophils play a major role in innate immune defense and are crucial in the injury-induced immunological response, we aimed to investigate systemic neutrophil-derived immunomodulators in trauma patients. Therefore, serum levels of neutrophil elastase (NE), myeloperoxidase (MPO), and citrullinated histone H3 (CitH3) were quantified in patients with injury severity scores above 15. Additionally, leukocyte, platelet, fibrinogen, and CRP levels were assessed. Lastly, we analyzed the association of neutrophil-derived factors with clinical severity scoring systems. Although the release of MPO, NE, and CitH3 was not predictive of mortality, we found a remarkable increase in MPO and NE in trauma patients as compared with healthy controls. We also found significantly increased levels of MPO and NE on days 1 and 5 after initial trauma in critically injured patients. Taken together, our data suggest a role for neutrophil activation and NETosis in trauma. Targeting exacerbated neutrophil activation might represent a new therapeutic option for critically injured patients.

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Section: Introductionsupporting

confidence: 92%

“…Nineteen patients (18%) died during hospital stay. Injured patients presented with a median ISS of 34 [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] 2), but these differences were not signi cant.…”

Section: Study Population Characteristicsmentioning

confidence: 99%

Elevation of neutrophil-derived factors in patients after multiple trauma

Lingitz

Wollner

Bauer

et al. 2022

Preprint

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“…Neutrophils release NETs, which are web-like extrusions that may kill microorganisms directly. NETs play a crucial regulatory function in the development of severe inflammatory illnesses [ 147 , 148 ]. SAP-induced MODS is hypothesized to be exacerbated by the excessive formation of NETs [ 149 ].…”

Section: Exosome-specific Proteinsmentioning

confidence: 99%

Fighting Fire with Fire: Exosomes and Acute Pancreatitis-Associated Acute Lung Injury

et al. 2022

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Acute pancreatitis (AP) is a prevalent clinical condition of the digestive system, with a growing frequency each year. Approximately 20% of patients suffer from severe acute pancreatitis (SAP) with local consequences and multi-organ failure, putting a significant strain on patients’ health insurance. According to reports, the lungs are particularly susceptible to SAP. Acute respiratory distress syndrome, a severe type of acute lung injury (ALI), is the primary cause of mortality among AP patients. Controlling the mortality associated with SAP requires an understanding of the etiology of AP-associated ALI, the discovery of biomarkers for the early detection of ALI, and the identification of potentially effective drug treatments. Exosomes are a class of extracellular vesicles with a diameter of 30–150 nm that are actively released into tissue fluids to mediate biological functions. Exosomes are laden with bioactive cargo, such as lipids, proteins, DNA, and RNA. During the initial stages of AP, acinar cell-derived exosomes suppress forkhead box protein O1 expression, resulting in M1 macrophage polarization. Similarly, macrophage-derived exosomes activate inflammatory pathways within endothelium or epithelial cells, promoting an inflammatory cascade response. On the other hand, a part of exosome cargo performs tissue repair and anti-inflammatory actions and inhibits the cytokine storm during AP. Other reviews have detailed the function of exosomes in the development of AP, chronic pancreatitis, and autoimmune pancreatitis. The discoveries involving exosomes at the intersection of AP and acute lung injury (ALI) are reviewed here. Furthermore, we discuss the therapeutic potential of exosomes in AP and associated ALI. With the continuous improvement of technological tools, the research on exosomes has gradually shifted from basic to clinical applications. Several exosome-specific non-coding RNAs and proteins can be used as novel molecular markers to assist in the diagnosis and prognosis of AP and associated ALI.

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“…That chart review and use of dapsone in ARDS was based on the extensive body of data on dapsone’s clinical effects of reducing neutrophil-mediated tissue damage in other human diseases, prominently the neutrophilic dermatoses, plus the well-established tissue-destructive role of neutrophils seen in fatal COVID-19 cases as briefly reviewed below [ 3 , 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Dapsone Lowers Neutrophil to Lymphocyte Ratio and Mortality in COVID-19 Patients Admitted to the ICU

Kanwar¹,

Khattak²,

Kast³

2022

IJMS

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Some physicians use dapsone as part of the standard treatment of severe COVID-19 patients entering the ICU, though some do not. To obtain an indication of whether dapsone is helping or not, we undertook a retrospective chart review of 29 consecutive ICU COVID-19 patients receiving dapsone and 30 not receiving dapsone. As we previously reported, of those given dapsone, 9/29 (30%) died, while of those not given dapsone, 18/30 (60%) died. We looked back on that data set to determine if there might be basic laboratory findings in these patients that might give an indication of a mechanism by which dapsone was acting. We found that the neutrophil-to-lymphocyte ratio decreased in 48% of those given dapsone and in 30% of those not given dapsone. We concluded that dapsone might be lowering that ratio. We then reviewed collected data on neutrophil related inflammation pathways on which dapsone might act as presented here. As this was not a controlled study, many variables prevent drawing any conclusions from this work; a formal, randomized controlled study of dapsone in severe COVID-19 is warranted.

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The role of neutrophil extracellular traps in acute lung injury

Cited by 69 publications

References 178 publications

Elevation of neutrophil-derived factors in patients after multiple trauma

Elevation of neutrophil-derived factors in patients after multiple trauma

Fighting Fire with Fire: Exosomes and Acute Pancreatitis-Associated Acute Lung Injury

Dapsone Lowers Neutrophil to Lymphocyte Ratio and Mortality in COVID-19 Patients Admitted to the ICU

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