Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy

Keir, Holly R.; Chalmers, James D.

doi:10.1183/16000617.0241-2021

Cited by 66 publications

(42 citation statements)

References 160 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These cells respond rapidly to infection and injury in various tissues. They represent the first line of defense and utilize multiple mechanisms of oxygen-dependent and oxygen-independent processes to protect against infection, including phagocytosis, cytokine secretion, and reactive oxygen species production [ 60 , 61 ]. Thus, neutrophils represent a potential target for the development of novel anti-inflammatory therapeutics.…”

Section: Resultsmentioning

confidence: 99%

Neutrophil Immunomodulatory Activity of Farnesene, a Component of Artemisia dracunculus Essential Oils

Schepetkin

Özek

et al. 2022

Pharmaceuticals

View full text Add to dashboard Cite

Despite their reported therapeutic properties, not much is known about the immunomodulatory activity of essential oils present in Artemisia species. We isolated essential oils from the flowers and leaves of five Artemisia species: A. tridentata, A. ludoviciana, A. dracunculus, A. frigida, and A. cana. The chemical composition of the Artemisia essential oil samples had similarities and differences as compared to those previously reported in the literature. The main components of essential oils obtained from A. tridentata, A. ludoviciana, A. frigida, and A. cana were camphor (23.0–51.3%), 1,8-cineole (5.7–30.0%), camphene (1.6–7.7%), borneol (2.3–14.6%), artemisiole (1.2–7.5%), terpinen-4-ol (2.0–6.9%), α-pinene (0.8–3.9%), and santolinatriene (0.7–3.5%). Essential oils from A. dracunculus were enriched in methyl chavicol (38.8–42.9%), methyl eugenol (26.1–26.4%), terpinolene (5.5–8.8%), (E/Z)-β-ocimene (7.3–16.0%), β-phellandrene (1.3–2.2%), p-cymen-8-ol (0.9–2.3%), and xanthoxylin (1.2–2.2%). A comparison across species also demonstrated that some compounds were present in only one Artemisia species. Although Artemisia essential oils were weak activators of human neutrophils, they were relatively more potent in inhibiting subsequent neutrophil Ca2+ mobilization with N-formyl peptide receptor 1 (FPR1) agonist fMLF- and FPR2 agonist WKYMVM, with the most potent being essential oils from A. dracunculus. Further analysis of unique compounds found in A. dracunculus showed that farnesene, a compound with a similar hydrocarbon structure as lipoxin A4, inhibited Ca2+ influx induced in human neutrophils by fMLF (IC50 = 1.2 μM), WKYMVM (IC50 = 1.4 μM), or interleukin 8 (IC50 = 2.6 μM). Pretreatment with A. dracunculus essential oils and farnesene also inhibited human neutrophil chemotaxis induced by fMLF, suggesting these treatments down-regulated human neutrophil responses to inflammatory chemoattractants. Thus, our studies have identified farnesene as a potential anti-inflammatory modulator of human neutrophils.

show abstract

Section: Resultsmentioning

confidence: 99%

Neutrophil Immunomodulatory Activity of Farnesene, a Component of Artemisia dracunculus Essential Oils

Schepetkin

Özek

et al. 2022

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…However, when the NET formation is dysregulated and therefore excessive or continuous, it promotes tissue damage and inflammation. 28 An example of this pathogenic role of NET in asthma is the study by He et al . 29 They showed that when a murine model of asthma is challenged with intratracheal < 2.5-µm particulate matter (PM2.5), it increases asthma severity.…”

Section: Neutrophils In Chronic Respiratory Diseasesmentioning

confidence: 99%

The Dynamic Contribution of Neutrophils in the Chronic Respiratory Diseases

Ham

Kim

et al. 2022

Allergy Asthma Immunol Res

View full text Add to dashboard Cite

Asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis are representative chronic respiratory diseases (CRDs). Although they differ in terms of disease presentation, they are all thought to arise from unresolved inflammation. Neutrophils are not only the first responders to acute inflammation, but they also help resolve the inflammation. Notably, emerging clinical studies show that CRDs are associated with systemic and local elevation of neutrophils. Moreover, murine studies suggest that airway-infiltrating neutrophils not only help initiate airway inflammation but also prolong the inflammation. Given this background, this review describes neutrophil-mediated immune responses in CRDs and summarizes the completed, ongoing, and potential clinical trials that test the therapeutic value of targeting neutrophils in CRDs. The review also clarifies the importance of understanding how neutrophils interact with other immune cells and how these interactions contribute to chronic inflammation in specific CRDs. This information may help identify future therapeutic strategies for CRDs.

show abstract

“…Of note, low-density neutrophils have been described to be particularly prone to release NETs (46)(47)(48). NETs have been identified by several studies as important players in respiratory disorders of the lower airways in man (49) and mice (28,50,51), where they can induce important damage of the lung tissue (52,53), aberrantly activate other innate immune cells (25, [54][55][56] or favor thrombi formation (26). In asthma, NETs can facilitate the induction of type 2 immunity associated with allergic asthma (28,50) and favor differentiation of helper type 17 T (Th17) cells (57) and skewing toward neutrophilic inflammation in neutrophilic asthma (58).…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Extracellular Traps Are Found in Bronchoalveolar Lavage Fluids of Horses With Severe Asthma and Correlate With Asthma Severity

et al. 2022

View full text Add to dashboard Cite

Asthma encompasses a spectrum of heterogenous immune-mediated respiratory disorders sharing a similar clinical pattern characterized by cough, wheeze and exercise intolerance. In horses, equine asthma can be subdivided into severe or moderate asthma according to clinical symptoms and the extent of airway neutrophilic inflammation. While severe asthmatic horses are characterized by an elevated neutrophilic inflammation of the lower airways, cough, dyspnea at rest and high mucus secretion, horses with moderate asthma show a milder neutrophilic inflammation, exhibit intolerance to exercise but no labored breathing at rest. Yet, the physiopathology of different phenotypes of equine asthma remains poorly understood and there is a need to elucidate the underlying mechanisms tailoring those phenotypes in order to improve clinical management and elaborate novel therapeutic strategies. In this study, we sought to quantify the presence of neutrophil extracellular traps (NETs) in bronchoalveolar lavage fluids (BALF) of moderate or severe asthmatic horses and healthy controls, and assessed whether NETs correlated with disease severity. To this end, we evaluated the amounts of NETs by measuring cell-free DNA and MPO-DNA complexes in BALF supernatants or by quantifying NETs release by BALF cells by confocal microscopy. We were able to unequivocally identify elevated NETs levels in BALF of severe asthmatic horses as compared to healthy controls or moderate asthmatic horses. Moreover, we provided evidence that BALF NETs release was a specific feature seen in severe equine asthma, as opposed to moderate asthma, and correlated with disease severity. Finally, we showed that NETs could act as a predictive factor for severe equine asthma. Our study thus uniquely identifies NETs in BALF of severe asthmatic horses using three distinct methods and supports the idea that moderate and severe equine asthma do not rely on strictly similar pathophysiological mechanisms. Our data also suggest that NETs represent a relevant biomarker, a putative driver and a potential therapeutic target in severe asthma disease.

show abstract

Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy

Cited by 66 publications

References 160 publications

Neutrophil Immunomodulatory Activity of Farnesene, a Component of Artemisia dracunculus Essential Oils

Neutrophil Immunomodulatory Activity of Farnesene, a Component of Artemisia dracunculus Essential Oils

The Dynamic Contribution of Neutrophils in the Chronic Respiratory Diseases

Neutrophil Extracellular Traps Are Found in Bronchoalveolar Lavage Fluids of Horses With Severe Asthma and Correlate With Asthma Severity

Contact Info

Product

Resources

About