Neutrophils in chronic inflammatory diseases

Herrero-Cervera, Andrea; Soehnlein, Oliver; Kenne, Ellinor

doi:10.1038/s41423-021-00832-3

Cited by 205 publications

(91 citation statements)

References 209 publications

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“…Specifically, there is evidence of continuous recruitment of neutrophils to sites of inflammation, where they add to the chronic inflammatory responses by releasing proteases, forming neutrophil extracellular traps (NETs), and activating other immune cells. 16 …”

Section: Introductionmentioning

confidence: 99%

The Dynamic Contribution of Neutrophils in the Chronic Respiratory Diseases

Ham

Kim

et al. 2022

Allergy Asthma Immunol Res

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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.

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Section: Introductionmentioning

confidence: 99%

The Dynamic Contribution of Neutrophils in the Chronic Respiratory Diseases

Ham

Kim

et al. 2022

Allergy Asthma Immunol Res

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“…The extent to which endothelial dysfunction and sterile inflammation are mechanistically linked remains largely unknown. One inflammatory feature in DKD is increased neutrophil activation [ 8 ], yet the mechanism through which activated neutrophils orchestrate vascular injury in DKD remains to be shown.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Extracellular Traps Promote NLRP3 Inflammasome Activation and Glomerular Endothelial Dysfunction in Diabetic Kidney Disease

et al. 2022

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Diabetes mellitus is a metabolic disease largely due to lifestyle and nutritional imbalance, resulting in insulin resistance, hyperglycemia and vascular complications. Diabetic kidney disease (DKD) is a major cause of end-stage renal failure contributing to morbidity and mortality worldwide. Therapeutic options to prevent or reverse DKD progression are limited. Endothelial and glomerular filtration barrier (GFB) dysfunction and sterile inflammation are associated with DKD. Neutrophil extracellular traps (NETs), originally identified as an innate immune mechanism to combat infection, have been implicated in sterile inflammatory responses in non-communicable diseases. However, the contribution of NETs in DKD remains unknown. Here, we show that biomarkers of NETs are increased in diabetic mice and diabetic patients and that these changes correlate with DKD severity. Mechanistically, NETs promote NLRP3 inflammasome activation and glomerular endothelial dysfunction under high glucose stress in vitro and in vivo. Inhibition of NETs (PAD4 inhibitor) ameliorate endothelial dysfunction and renal injury in DKD. Taken together, NET-induced sterile inflammation promotes diabetes-associated endothelial dysfunction, identifying a new pathomechanism contributing to DKD. Inhibition of NETs may be a promising therapeutic strategy in DKD.

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“…The production of nitrite in IPEs may arise from locally produced NO resulting from inflammation caused by infection [ 32 ], as evidenced by a neutrophil-dominant PE in the clinical scenario (neutrophils, GM %: 21% for parapneumonic effusions and 33% for empyema). It is well-known that neutrophils are normally the first responders to inflammation [ 33 ]. Neutrophils can kill invading pathogens by enhancing reactive oxygen species (ROS) and NO generation.…”

Section: Discussionmentioning

confidence: 99%

Elevated Nitrite/Nitrate Ratio as a Potential Biomarker for the Differential Diagnosis of Pleural Effusions

et al. 2022

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Pleural effusions (PEs) are common in clinical practice and can be due to many different underlying diseases such as cancer, congestive heart failure, or pneumonia. An accurate differential diagnostic categorization is essential, as the treatment and prognosis of PEs largely depend on its cause. In this study, we tested the hypothesis that nitrite and nitrate concentrations in PEs are associated with the inflammation and infection conditions. We therefore measured the nitrite and nitrate levels in 143 PE samples using a sensitive liquid chromatography-tandem mass spectrometry method and investigated their diagnostic potential in differentiating PEs. The results showed that nitrite concentrations and nitrite/nitrate ratios were higher in exudates than in transudates (NO2−: 2.12 vs. 1.49 μM; NO2−/NO3−: 23.3 vs. 14.0). Both the nitrite concentrations and the nitrite/nitrate ratios were positively correlated with the three Light’s criteria. Moreover, the receiver operating characteristic curve analysis revealed that the nitrite/nitrate ratio with an area under the curve of 0.71 could be a potential diagnostic biomarker in separating infectious PEs (IPEs) from other types of PEs. Taken together, the nitrite/nitrate ratio not only reflected the statuses of inflammation, but also the nitrate reduction by pathogenic bacteria infection in the pleural cavity. The nitrite/nitrate ratio could be a better biomarker in the differential diagnosis of PEs than the nitrite concentration alone.

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Neutrophils in chronic inflammatory diseases

Cited by 205 publications

References 209 publications

The Dynamic Contribution of Neutrophils in the Chronic Respiratory Diseases

The Dynamic Contribution of Neutrophils in the Chronic Respiratory Diseases

Neutrophil Extracellular Traps Promote NLRP3 Inflammasome Activation and Glomerular Endothelial Dysfunction in Diabetic Kidney Disease

Elevated Nitrite/Nitrate Ratio as a Potential Biomarker for the Differential Diagnosis of Pleural Effusions

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