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10.1038/ncomms10555

http://scihub22266oqcxt.onion/10.1038/ncomms10555
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suck abstract from ncbi


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pmid26877061
      Nat+Commun 2016 ; 7 (ä): 10555
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  • Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1? secretion in response to ATP #MMPMID26877061
  • Karmakar M ; Katsnelson MA ; Dubyak GR ; Pearlman E
  • Nat Commun 2016[Feb]; 7 (ä): 10555 PMID26877061 show ga
  • Although extracellular ATP is abundant at sites of inflammation, its role in activating inflammasome signalling in neutrophils is not well characterized. In the current study, we demonstrate that human and murine neutrophils express functional cell-surface P2X7R, which leads to ATP-induced loss of intracellular K(+), NLRP3 inflammasome activation and IL-1? secretion. ATP-induced P2X7R activation caused a sustained increase in intracellular [Ca(2+)], which is indicative of P2X7R channel opening. Although there are multiple polymorphic variants of P2X7R, we found that neutrophils from multiple donors express P2X7R, but with differential efficacies in ATP-induced increase in cytosolic [Ca(2+)]. Neutrophils were also the predominant P2X7R-expressing cells during Streptococcus pneumoniae corneal infection, and P2X7R was required for bacterial clearance. Given the ubiquitous presence of neutrophils and extracellular ATP in multiple inflammatory conditions, ATP-induced P2X7R activation and IL-1? secretion by neutrophils likely has a significant, wide ranging clinical impact.
  • |Adenosine Triphosphate/*immunology [MESH]
  • |Animals [MESH]
  • |Blotting, Western [MESH]
  • |Calcium/metabolism [MESH]
  • |Carrier Proteins/genetics/*immunology [MESH]
  • |Disease Models, Animal [MESH]
  • |Enzyme-Linked Immunosorbent Assay [MESH]
  • |Eye Infections, Bacterial/immunology [MESH]
  • |Flow Cytometry [MESH]
  • |Humans [MESH]
  • |Inflammasomes/*immunology [MESH]
  • |Interleukin-1beta/*metabolism [MESH]
  • |Keratitis/immunology [MESH]
  • |Mice [MESH]
  • |Mice, Inbred C57BL [MESH]
  • |Mice, Knockout [MESH]
  • |Microscopy, Fluorescence [MESH]
  • |NLR Family, Pyrin Domain-Containing 3 Protein [MESH]
  • |Neutrophils/drug effects/*immunology/metabolism [MESH]
  • |Potassium/metabolism [MESH]
  • |Purinergic P2X Receptor Antagonists/pharmacology [MESH]
  • |Receptors, Purinergic P2X7/*immunology [MESH]
  • |Spectrophotometry, Atomic [MESH]


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