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10.1038/ncomms15196

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suck abstract from ncbi


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pmid28497779
      Nat+Commun 2017 ; 8 (ä): 15196
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  • L-selectin mechanochemistry restricts neutrophil priming in vivo #MMPMID28497779
  • Liu Z ; Yago T ; Zhang N ; Panicker SR ; Wang Y ; Yao L ; Mehta-D'souza P ; Xia L ; Zhu C ; McEver RP
  • Nat Commun 2017[May]; 8 (ä): 15196 PMID28497779 show ga
  • Circulating neutrophils must avoid premature activation to prevent tissue injury. The leukocyte adhesion receptor L-selectin forms bonds with P-selectin glycoprotein ligand-1 (PSGL-1) on other leukocytes and with peripheral node addressin (PNAd) on high endothelial venules. Mechanical forces can strengthen (catch) or weaken (slip) bonds between biological molecules. How these mechanochemical processes influence function in vivo is unexplored. Here we show that mice expressing an L-selectin mutant (N138G) have altered catch bonds and prolonged bond lifetimes at low forces. Basal lymphocyte homing and neutrophil recruitment to inflamed sites are normal. However, circulating neutrophils form unstable aggregates and are unexpectedly primed to respond robustly to inflammatory mediators. Priming requires signals transduced through L-selectin N138G after it engages PSGL-1 or PNAd. Priming enhances bacterial clearance but increases inflammatory injury and enlarges venous thrombi. Thus, L-selectin mechanochemistry limits premature activation of neutrophils. Our results highlight the importance of probing how mechanochemistry functions in vivo.
  • |Animals [MESH]
  • |Antigens, Surface/metabolism [MESH]
  • |Biomechanical Phenomena/*immunology [MESH]
  • |Cells, Cultured [MESH]
  • |Endothelium, Vascular/cytology/immunology [MESH]
  • |Escherichia coli/immunology [MESH]
  • |Gene Knock-In Techniques [MESH]
  • |L-Selectin/genetics/*metabolism [MESH]
  • |Lymphocytes/immunology [MESH]
  • |Membrane Glycoproteins/*metabolism [MESH]
  • |Membrane Proteins/metabolism [MESH]
  • |Mice [MESH]
  • |Mice, Inbred C57BL [MESH]
  • |Mice, Knockout [MESH]
  • |Neutrophil Activation/*immunology [MESH]
  • |Neutrophils/*immunology [MESH]


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