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Blood cells communicate remotely via an NMDA receptor-mediated glutamatergic chain-reaction

Kopach, O.; Sylantyev, S.; Bard, L.; Michaluk, P.; Gutierrez del Arroyo, A.; Ackland, G. L.; Rusakov, D. A.

2022-02-26 cell biology
10.1101/2022.02.25.482046 bioRxiv
Show abstract

Neutrophils are white blood cells that are critical to the acute inflammatory and adaptive immune responses. Their swarming-pattern behaviour is controlled by multiple cellular cascades involving calcium-dependent release of various signalling 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 mobilisation induced by stimulating one neutrophil can trigger an NMDA receptor-driven membrane current and calcium signal in neighbouring neutrophils. We employ an enzymatic-based imaging assay to image, in real time, glutamate release from neutrophils induced by glutamate released from their neighbours. These observations provide direct evidence for a positive-feedback inter-neutrophil communication that could contribute to mechanisms regulating communal neutrophil behaviour.

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