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10.4049/jimmunol.1300436

http://scihub22266oqcxt.onion/10.4049/jimmunol.1300436
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23904163!ä!23904163

suck abstract from ncbi


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pmid23904163      J+Immunol 2013 ; 191 (5): 2647-56
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  • Macrophage clearance of neutrophil extracellular traps is a silent process #MMPMID23904163
  • Farrera C; Fadeel B
  • J Immunol 2013[Sep]; 191 (5): 2647-56 PMID23904163show ga
  • 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-1beta, IL-6, and TNF-alpha 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.
  • |Blotting, Western[MESH]
  • |Complement C1q/immunology/metabolism[MESH]
  • |Deoxyribonuclease I/immunology/metabolism[MESH]
  • |Extracellular Space/immunology[MESH]
  • |Fluorescent Antibody Technique[MESH]
  • |Humans[MESH]
  • |Macrophages/*immunology/metabolism[MESH]
  • |Microscopy, Confocal[MESH]
  • |Microscopy, Electron, Scanning[MESH]
  • |Neutrophil Activation/immunology[MESH]
  • |Neutrophils/*immunology/metabolism[MESH]


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