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- Consol Farrera
- Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet , 171 77 Stockholm,
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- Bengt Fadeel
- Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet , 171 77 Stockholm,
書誌事項
- 公開日
- 2013-09-01
- 権利情報
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- https://academic.oup.com/pages/standard-publication-reuse-rights
- DOI
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- 10.4049/jimmunol.1300436
- 公開者
- Oxford University Press (OUP)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>Neutrophil extracellular traps (NETs) facilitate the extracellular killing of pathogens. However, in recent years, excessive NET formation has been implicated in several pathological conditions. Indeed, NETs that are not removed from tissues or from the circulation might serve to trigger autoimmune responses. We observed that physiological amounts of DNase I do not suffice to completely degrade NETs in vitro, suggesting that additional mechanisms are required for the removal of these extracellular structures. We show in this article that human monocyte–derived macrophages are able to engulf NETs in a cytochalasin D–dependent manner, indicating that this is an active, endocytic process. Furthermore, preprocessing of NETs by DNase I facilitated their clearance by macrophages. In addition, both recombinant C1q and endogenous C1q derived from human serum were found to opsonize NETs, and this facilitated NET clearance. Upon internalization, NETs were apparently degraded in lysosomes, as treatment with chloroquine led to accumulation of extranuclear DNA in human monocyte–derived macrophages. Finally, uptake of NETs alone did not induce proinflammatory cytokine secretion, whereas LPS-induced production of IL-1β, IL-6, and TNF-α was promoted by the uptake of NETs. In summary, we show that macrophages are capable of clearance of NETs and that this occurs in an immunologically silent manner.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 191 (5), 2647-2656, 2013-09-01
Oxford University Press (OUP)