Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils—The Current Knowledge, Pharmacological Modulation and Future Prospects

Gierlikowska, Barbara; Stachura, Albert; Gierlikowski, Wojciech; Demkow, Urszula

doi:10.3389/fphar.2021.666732

Cited by 48 publications

(40 citation statements)

References 249 publications

(281 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These structural changes could be attributed to the bactericidal activity of neutrophils, which is important for limiting microbial invasion. 25 In patients with infected and delayed healing diabetic ulcers, NETs identified by citrullinated histone 3 are negatively correlated with wound healing. 26 Activation of the Nod-like receptor protein (NLRP) 3 inflammasome and interleukin-1β release stimulated by NETs is the mechanism underlying delayed healing.…”

Section: Discussionmentioning

confidence: 99%

“…The prominent degranulation of neutrophils and enrichment of related gene sets were observed in our mouse model. These structural changes could be attributed to the bactericidal activity of neutrophils, which is important for limiting microbial invasion 25 . In patients with infected and delayed healing diabetic ulcers, NETs identified by citrullinated histone 3 are negatively correlated with wound healing 26 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Neutrophils and their extracellular traps impair ablative fractional carbon dioxide laser‐induced dermal remolding in mice

et al. 2022

View full text Add to dashboard Cite

Objectives: Ablative fractional CO 2 laser (AFL) therapy is an effective intervention to induce dermal remodeling. AFL treatment of the skin triggers the recruitment of immune cells, with neutrophils dominating the early phase. However, the role of recruited neutrophils in AFL-induced microinjuries and their subsequent dermal remodeling capacity remains elusive. Materials and Methods: A mouse model of AFL-induced dermal remodeling was established. RNA sequencing was used to identify the prominent features of AFL-treated tissues. Histological analysis, including H&E and Masson staining, ultrastructure observation by transmission microscopy, immunofluorescence, and quantitative real-time polymerase chain reaction were used for dermal remodeling analysis. Moreover, AFL-treated mice were intraperitoneally injected with antimouse Ly6G antibodies to deplete neutrophils. Neutrophil extracellular traps (NETs) were explored using immunofluorescence, transmission microscopy, and in vitro coculture experiments. Results: Dermal remodeling, characterized by an increased number of CD31-positve vessels and elevated messenger RNA (mRNA) expression of genes encoding transforming growth factor-β (TGF-β), collagen I, and collagen III, was observed at 15 days after AFL treatment. In the AFL-induced inflammation phase, RNA sequencing identified neutrophil chemotaxis, and degranulation genes were significantly enriched. Histology and immunofluorescence staining of human and mouse tissues harvested at Day 1 after AFL treatment revealed significant neutrophil infiltration surrounding thermal-induced microinjuries. Neutrophil depletion decreased the expression of stressrelated genes such as S100A8 and S100A9 in the early phase following AFL treatment. Importantly, neutrophil depletion enhanced dermal remodeling at Day 15, as reflected by enrichment of the extracellular matrix and collagen biosynthesis genes based on RNA sequencing. Moreover, increased collagen I, collagen III, and TGF-β mRNA expression, increased cell proliferation, and vascularity were observed. Interestingly, NETs, which could be induced by AFL-treated fibroblasts in vitro, were identified in both human and mouse tissues on Day 1 after AFL treatment. Conclusions: AFL-treated human and mouse skin recruited a large number of neutrophils. The neutrophil surge impaired dermal remodeling in mice. The microenvironment and fibroblast functional modulation mediated by neutrophil degranulation and NET formation were determined to be the underlying mechanisms. Our results indicate that modification of infiltrated neutrophil activity might be a potential therapeutic target for AFL-induced dermal remodeling.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neutrophils and their extracellular traps impair ablative fractional carbon dioxide laser‐induced dermal remolding in mice

et al. 2022

View full text Add to dashboard Cite

show abstract

“…These occlusions drive the pathophysiology and increase the severity of many diseases, including COVID-19, chole- and sialolithiasis, dry eye disease, and probably many others. Therefore, it is critical to developing new effective therapeutic strategies directed to control either the accumulation of NETs or improving their clearance at specific anatomic locations [ 26 , 116 ]. NETs-inducing agents are diverse, and the formation mechanisms of NETs vary depending on these triggering agents.…”

Section: Therapeutic Approaches To Prevent Nets-driven Occlusionsmentioning

confidence: 99%

Neutrophil Extracellular Trap-Driven Occlusive Diseases

Yaykaşlı

Schauer

Muñoz

et al. 2021

Cells

View full text Add to dashboard Cite

The enlightenment of the formation of neutrophil extracellular traps (NETs) as a part of the innate immune system shed new insights into the pathologies of various diseases. The initial idea that NETs are a pivotal defense structure was gradually amended due to several deleterious effects in consecutive investigations. NETs formation is now considered a double-edged sword. The harmful effects are not limited to the induction of inflammation by NETs remnants but also include occlusions caused by aggregated NETs (aggNETs). The latter carries the risk of occluding tubular structures like vessels or ducts and appear to be associated with the pathologies of various diseases. In addition to life-threatening vascular clogging, other occlusions include painful stone formation in the biliary system, the kidneys, the prostate, and the appendix. AggNETs are also prone to occlude the ductal system of exocrine glands, as seen in ocular glands, salivary glands, and others. Last, but not least, they also clog the pancreatic ducts in a murine model of neutrophilia. In this regard, elucidating the mechanism of NETs-dependent occlusions is of crucial importance for the development of new therapeutic approaches. Therefore, the purpose of this review is to address the putative mechanisms of NETs-associated occlusions in the pathogenesis of disease, as well as prospective treatment modalities.

show abstract

“…They are effector cells of the innate immune system and are active in inflammation. 1 , 2 Neutrophils have antimicrobial activity mediated by reactive oxygen intermediates and hydrolases capable of clearing invading pathogens, which places them in the first line of defense against bacteria and fungi. 3 Phagocytosis of invading pathogens by neutrophils is an efficient defense against infectious diseases, involves particles that are larger than 0.5 µM in diameter, and is mainly performed by professional phagocytes such as neutrophils and macrophages.…”

Section: Introductionmentioning

confidence: 99%

“…They are terminally differentiated cells that are constantly renewed by production in the bone marrow. They are effector cells of the innate immune system and are active in inflammation 1,2 . Neutrophils have antimicrobial activity mediated by reactive oxygen intermediates and hydrolases capable of clearing invading pathogens, which places them in the first line of defense against bacteria and fungi 3 .…”

Section: Introductionmentioning

confidence: 99%

PGE2 inhibits neutrophil phagocytosis through the EP2R–cAMP–PTEN pathway

Wang

Wei

et al. 2022

Immunity Inflam & Disease

View full text Add to dashboard Cite

Prostaglandin E2 (PGE2) is a potent lipid mediator of inflammation that modulates immune cell function by binding to unique G protein‐coupled receptors (EP receptors). PGE2 production increases during microbial infection and inflammation. In this study, we assessed the effect of PGE2 on the phagocytosis of bacteria by neutrophils, which are key players during infection and inflammation. We also looked for specific EP receptor signaling pathways that contributed to the neutrophil phagocytic activity. PGE2 (50–1000 ng/ml) inhibited the phagocytosis of Escherichia coli by HL‐60 human neutrophils in a concentration‐dependent manner. Inhibition of neutrophil phagocytosis by PGE2 correlated with increased intracellular cyclic adenosine monophosphate (cAMP) production, and forskolin, an adenosyl cyclase agonist, confirmed the inhibitory effect of cAMP stimulation on neutrophil phagocytosis. The expression of EP2 receptors by HL‐60 cells was confirmed by western blot analysis, and selective agonism of EP2 receptors mimicked the inhibition of phagocytosis by PGE2. The EP2 receptor antagonist AH‐6089 partially blocked the inhibition of neutrophil phagocytosis PGE2. Specific inhibition of phosphatase and tensin homolog (PTEN) enzyme attenuated the inhibition of neutrophil phagocytosis by PGE2, and both PGE2 and increased intracellular cAMP increased neutrophil PTEN activity, which was associated with decreased PTEN phosphorylation. The results support negative regulation of the antimicrobial activity of neutrophils (i.e., phagocytosis), which has important implications for the future management of bacterial infections.

show abstract

Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils—The Current Knowledge, Pharmacological Modulation and Future Prospects

Cited by 48 publications

References 249 publications

Neutrophils and their extracellular traps impair ablative fractional carbon dioxide laser‐induced dermal remolding in mice

Neutrophils and their extracellular traps impair ablative fractional carbon dioxide laser‐induced dermal remolding in mice

Neutrophil Extracellular Trap-Driven Occlusive Diseases

PGE2 inhibits neutrophil phagocytosis through the EP2R–cAMP–PTEN pathway

Contact Info

Product

Resources

About