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10.1182/blood.2021013422

http://scihub22266oqcxt.onion/10.1182/blood.2021013422
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34814186!8612755!34814186
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suck abstract from ncbi

pmid34814186      Blood 2022 ; 139 (8): 1222-1233
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  • Resolvin T-series reduce neutrophil extracellular traps #MMPMID34814186
  • Chiang N; Sakuma M; Rodriguez AR; Spur BW; Irimia D; Serhan CN
  • Blood 2022[Feb]; 139 (8): 1222-1233 PMID34814186show ga
  • The newly identified 13-series (T-series) resolvins (RvTs) regulate phagocyte functions and accelerate resolution of infectious inflammation. Because severe acute respiratory syndrome coronavirus 2 elicits uncontrolled inflammation involving neutrophil extracellular traps (NETs), we tested whether stereochemically defined RvTs regulate NET formation. Using microfluidic devices capturing NETs in phorbol 12-myristate 13-acetate-stimulated human whole blood, the RvTs (RvT1-RvT4; 2.5 nM each) potently reduced NETs. With interleukin-1beta-stimulated human neutrophils, each RvT dose and time dependently decreased NETosis, conveying approximately 50% potencies at 10 nM, compared with a known NETosis inhibitor (10 muM). In a murine Staphylococcus aureus infection, RvTs (50 ng each) limited neutrophil infiltration, bacterial titers, and NETs. In addition, each RvT enhanced NET uptake by human macrophages; RvT2 was the most potent of the four RvTs, giving a >50% increase in NET-phagocytosis. As part of the intracellular signaling mechanism, RvT2 increased cyclic adenosine monophosphate and phospho-AMP-activated protein kinase (AMPK) within human macrophages, and RvT2-stimulated NET uptake was abolished by protein kinase A and AMPK inhibition. RvT2 also stimulated NET clearance by mouse macrophages in vivo. Together, these results provide evidence for novel pro-resolving functions of RvTs, namely reducing NETosis and enhancing macrophage NET clearance via a cyclic adenosine monophosphate-protein kinase A-AMPK axis. Thus, RvTs open opportunities for regulating NET-mediated collateral tissue damage during infection as well as monitoring NETs.
  • |Animals[MESH]
  • |COVID-19/immunology[MESH]
  • |Extracellular Traps/*immunology[MESH]
  • |Humans[MESH]
  • |Inflammation/immunology[MESH]
  • |Macrophages/immunology[MESH]
  • |Mice[MESH]
  • |Neutrophils/immunology[MESH]
  • |Phagocytosis[MESH]
  • |SARS-CoV-2/immunology[MESH]
  • |Staphylococcal Infections/*immunology[MESH]


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