Kopach, Olga;
              
      
            
                Sylantyev, Sergyi;
              
      
            
                Bard, Lucie;
              
      
            
                Michaluk, Piotr;
              
      
            
                Heller, Janosch P;
              
      
            
                Gutierrez del Arroyo, Ana;
              
      
            
                Ackland, Gareth L;
              
      
            
            
          
      
            
            
            ... Rusakov, Dmitri A; + view all
            
          
      
        
        
        
    
  
(2023)
  Human neutrophils communicate remotely via calcium-dependent glutamate-induced glutamate release.
iScience
, 26
       (7)
    
    
    
    , Article 107236.     10.1016/j.isci.2023.107236.
  
  
      
    
  
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 1-s2.0-S2589004223013135-main.pdf - Published Version Download (3MB) | Preview  | 
          
Abstract
Summary Neutrophils are white blood cells that are critical to acute inflammatory and adaptive immune responses. Their swarming-pattern behavior is controlled by multiple cellular cascades involving calcium-dependent release of various signaling molecules. Previous studies have reported that neutrophils express glutamate receptors and can release glutamate but evidence of direct neutrophil-neutrophil communication has been elusive. Here, we hold semi-suspended cultured human neutrophils in patch-clamp whole-cell mode to find that calcium mobilization induced by stimulating one neutrophil can trigger an N-methyl-D-aspartate (NMDA) receptor-driven membrane current and calcium signal in neighboring neutrophils. We employ an enzymatic-based imaging assay to image, in real time, glutamate release from neutrophils induced by glutamate released from their neighbors. These observations provide direct evidence for a positive-feedback inter-neutrophil communication that could contribute to mechanisms regulating communal neutrophil behavior.
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