New Aspects on the Structure of Neutrophil Extracellular Traps from Chronic Obstructive Pulmonary Disease and In Vitro Generation

Obermayer, Astrid; Stoiber, Walter; Krautgartner, Wolf‐Dietrich; Klappacher, Michaela; Kofler, Barbara; Steinbacher, Peter; Vitkov, Ljubomir; Grabcanovic-Musija, Fikreta; Studnicka, Michael

doi:10.1371/journal.pone.0097784

Cited by 82 publications

(84 citation statements)

References 43 publications

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“…NETs, however, also cause tissue damage in airway diseases characterized by P . aeruginosa infections (e.g., CF and COPD) [31, 32, 70]. Therefore, it is important to illuminate the cellular-molecular details of P .…”

Section: Discussionmentioning

confidence: 99%

Swimming Motility Mediates the Formation of Neutrophil Extracellular Traps Induced by Flagellated Pseudomonas aeruginosa

et al. 2016

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Pseudomonas aeruginosa is an opportunistic pathogen causing severe infections often characterized by robust neutrophilic infiltration. Neutrophils provide the first line of defense against P. aeruginosa. Aside from their defense conferred by phagocytic activity, neutrophils also release neutrophil extracellular traps (NETs) to immobilize bacteria. Although NET formation is an important antimicrobial process, the details of its mechanism are largely unknown. The identity of the main components of P. aeruginosa responsible for triggering NET formation is unclear. In this study, our focus was to identify the main bacterial factors mediating NET formation and to gain insight into the underlying mechanism. We found that P. aeruginosa in its exponential growth phase promoted strong NET formation in human neutrophils while its NET-inducing ability dramatically decreased at later stages of bacterial growth. We identified the flagellum as the primary component of P. aeruginosa responsible for inducing NET extrusion as flagellum-deficient bacteria remained seriously impaired in triggering NET formation. Purified P. aeruginosa flagellin, the monomeric component of the flagellum, does not stimulate NET formation in human neutrophils. P. aeruginosa-induced NET formation is independent of the flagellum-sensing receptors TLR5 and NLRC4 in both human and mouse neutrophils. Interestingly, we found that flagellar motility, not flagellum binding to neutrophils per se, mediates NET release induced by flagellated bacteria. Immotile, flagellar motor-deficient bacterial strains producing paralyzed flagella did not induce NET formation. Forced contact between immotile P. aeruginosa and neutrophils restored their NET-inducing ability. Both the motAB and motCD genetic loci encoding flagellar motor genes contribute to maximal NET release; however the motCD genes play a more important role. Phagocytosis of P. aeruginosa and superoxide production by neutrophils were also largely dependent upon a functional flagellum. Taken together, the flagellum is herein presented for the first time as the main organelle of planktonic bacteria responsible for mediating NET release. Furthermore, flagellar motility, rather than binding of the flagellum to flagellum-sensing receptors on host cells, is required for P. aeruginosa to induce NET release.

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Section: Discussionmentioning

confidence: 99%

Swimming Motility Mediates the Formation of Neutrophil Extracellular Traps Induced by Flagellated Pseudomonas aeruginosa

et al. 2016

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“…Tobacco smoke has been found to directly induce NET formation [14], possibly due to its LPS content. Additionally, nicotine directly induces NETosis [65-67], and it is not surprising that NETs have been found in COPD lungs [68]. As is the case in CF, also in COPD disease severity correlates to the amount of NETs, which is highest in phases of exacerbations [65].…”

Section: Lung Diseasesmentioning

confidence: 99%

Neutrophil Extracellular Traps in the Second Decade

2018

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Nearly 15 years after the first description of neutrophil extracellular traps (NETs), our knowledge concerning this structure has expanded considerably. Initially, NETs were considered solely an elaborate function of the innate immune system to combat invading microorganisms. Successively it became clear that NETs have farther-reaching capabilities. They are involved in a series of pathophysiological mechanisms ranging from inflammation to thrombosis where they fulfill essential functions when produced at the right site and the right time but can have a serious impact when generation or clearance of NETs is inadequately controlled. This review provides a concise overview on the far-reaching functions of NETs in health and disease.

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“…[954] It has a substantial impact on the quality of life and life expectancy, as well as currently being the third leading cause of mortality and the fifth leading cause of disability on a global scale. [5556]…”

Section: Neutrophil Extracellular Traps and Chronic Obstructive Pulmomentioning

confidence: 99%

Role of Neutrophil Extracellular Traps in Asthma and Chronic Obstructive Pulmonary Disease

Liu

Wang

et al. 2017

Chinese Medical Journal

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Objective:Asthma and chronic obstructive pulmonary disease (COPD) are representative chronic inflammatory airway diseases responsible for a considerable burden of disease. In this article, we reviewed the relationship between neutrophil extracellular traps (NETs) and chronic inflammatory airway diseases.Data Sources:Articles published up to January 1, 2017, were selected from the PubMed, Ovid Medline, Embase databases, with the keywords of “asthma” or “pulmonary disease, chronic obstructive”, “neutrophils” and “extracellular traps.”Study Selection:Articles were obtained and reviewed to analyze the role of NETs in asthma and COPD.Results:NETs are composed of extracellular DNA, histones, and granular proteins, which are released from activated neutrophils. Multiple studies have indicated that there are a large amount of NETs in the airways of asthmatics and COPD patients. NETs can engulf and kill invading pathogens in the host. However, disordered regulation of NET formation has shown to be involved in the development of asthma and COPD. An overabundance of NETs in the airways or lung tissue could cause varying degrees of damage to lung tissues by inducing the death of human epithelial and endothelial cells, and thus resulting in impairing pulmonary function and accelerating the progress of the disease.Conclusions:Excessive NETs accumulate in the airways of asthmatics and COPD patients. Although NETs play an essential role in the innate immune system against infection, excessive components of NETs can cause lung tissue damage and accelerate disease progression in asthmatics and COPD patients. These findings suggest that administration of NETs could be a novel approach to treat asthma and COPD. Mechanism studies, clinical practice, and strategies to regulate neutrophil activation or directly interrupt NET function in asthmatics and COPD patients are desperately needed.

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New Aspects on the Structure of Neutrophil Extracellular Traps from Chronic Obstructive Pulmonary Disease and In Vitro Generation

Cited by 82 publications

References 43 publications

Swimming Motility Mediates the Formation of Neutrophil Extracellular Traps Induced by Flagellated Pseudomonas aeruginosa

Swimming Motility Mediates the Formation of Neutrophil Extracellular Traps Induced by Flagellated Pseudomonas aeruginosa

Neutrophil Extracellular Traps in the Second Decade

Role of Neutrophil Extracellular Traps in Asthma and Chronic Obstructive Pulmonary Disease

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