Role and Therapeutic Targeting Strategies of Neutrophil Extracellular Traps in Inflammation

Li, Xiang; Xiao, Shanghua; Filipczak, Nina; Yalamarty, Satya Siva Kishan; Shang, Hongming; Zhang, Jing; Zheng, Qin

doi:10.2147/ijn.s418259

Cited by 12 publications

(5 citation statements)

References 223 publications

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“…As a granule protein, NE's vital physiological function is to degrade the phagocytosed molecules within the cells. 33 , 34 Besides that NE can promote inflammation response and damage vessel endothelial cells through increasing cytokine expression and release. 35 , 36 For this reason, the serum levels and activity of NE may reflect the degree of organ injury and disease severity.…”

Section: Discussionmentioning

confidence: 99%

The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis

Sun,

Li,

Deng

et al. 2024

Clinical Translational Sci

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To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non‐sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non‐sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non‐sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4–6), p = 0.008]. The serum levels of d‐lactate (p = 0.033), intestinal fatty acid‐binding protein (p = 0.005), interleukin‐6 (p = 0.001), white blood cells (p = 0.007), C‐reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non‐sivelestat group. The sivelestat group also demonstrated longer ICU‐free days [18 (0–22) vs. 13 (0–17), p = 0.004] and ventilator‐free days [22 (1–24) vs. 16 (1–19), p = 0.002] compared with the non‐sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.

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Section: Discussionmentioning

confidence: 99%

The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis

Sun,

Li,

Deng

et al. 2024

Clinical Translational Sci

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“…The first pathway, termed suicidal or lytic NETosis ( Figure 1 a ), occurs when stimulated by triggers such as phorbol 12-myristate 13-acetate (PMA) and extracellular microbes 6 , 14 - 16 . This pathway involves the stimulation of protein kinase C (PKC) and Raf-MEK-ERK signaling, activating NADPH oxidase (NOX) and the production of reactive oxygen species (ROS) in neutrophils 17 - 19 . Upon ROS stimulation, NE escapes from the granules and translocates to the nucleus, where NE cleaves histones and promotes chromatin decondensation.…”

Section: Pathways Of Net Formationmentioning

confidence: 99%

“…While neutrophils release NETs to capture pathogens, persistent infections, and inflammatory environments can lead to excessive NET production, thereby promoting the development of various inflammatory diseases. This is primarily mediated through the activation of inflammasomes 19 , 60 . Similarly, studies have found interactions between inflammasomes and NETs in cancer.…”

Section: Roles Of Nets In Breast Cancer Metastasismentioning

confidence: 99%

Neutrophil Extracellular Traps in Breast Cancer: Roles in Metastasis and Beyond

Xu,

Wang,

Zheng

et al. 2024

J. Cancer

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Despite advances in the treatment of breast cancer, the disease continues to exhibit high global morbidity and mortality. The importance of neutrophils in cancer development has been increasingly recognized. Neutrophil extracellular traps (NETs) are web-like structures released into the extracellular space by activated neutrophils, serving as a potential antimicrobial mechanism for capturing and eliminating microorganisms. The roles played by NETs in cancer development have been a subject of intense research in the last decade. In breast cancer, current evidence suggests that NETs are involved in various stages of cancer development, particularly during metastasis. In this review, we try to provide an updated overview of the roles played by NETs in breast cancer metastasis. These include: 1) facilitating systemic dissemination of cancer cells; 2) promoting cancer-associated inflammation; 3) facilitating cancer-associated thrombosis; 4) facilitating pre-metastatic niche formation; and 5) awakening dormant cancer cells. The translational implications of NETs in breast cancer treatment are also discussed. Understanding the relationship between NETs and breast cancer metastasis is expected to provide important insights for developing new therapeutic strategies for breast cancer patients.

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“…NETs are involved in various pathological conditions, such as diabetes, wound healing, atherosclerosis, coagulation disorders, and periodontitis. 15 , 16 Excessive numbers of NETs also have a significant impact on cancer development (Please see the Graphic Abstract). 17 …”

Section: Introductionmentioning

confidence: 99%

Neutrophil Extracellular Traps in Tumors and Potential Use of Traditional Herbal Medicine Formulations for Its Regulation

Li,

Hu,

Naeem

et al. 2024

IJN

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Neutrophil extracellular traps (NETs) are extracellular fibers composed of deoxyribonucleic acid (DNA) and decorated proteins produced by neutrophils. Recently, NETs have been associated with the development of many diseases, including tumors. Herein, we reviewed the correlation between NETs and tumors. In addition, we detailed active compounds from traditional herbal medicine formulations that inhibit NETs, related nanodrug delivery systems, and antibodies that serve as “guiding moieties” to ensure targeted delivery to NETs. Furthermore, we discussed the strategies used by pathogenic microorganisms to evade NETs.

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Role and Therapeutic Targeting Strategies of Neutrophil Extracellular Traps in Inflammation

Cited by 12 publications

References 223 publications

The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis

The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis

Neutrophil Extracellular Traps in Breast Cancer: Roles in Metastasis and Beyond

Neutrophil Extracellular Traps in Tumors and Potential Use of Traditional Herbal Medicine Formulations for Its Regulation

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