Human neutrophils communicate remotely via calcium-dependent glutamate-induced glutamate release
Olga Kopach,
Sergyi Sylantyev,
Lucie Bard,
Piotr Michaluk,
Janosch P. Heller,
Ana Gutierrez del Arroyo,
Gareth L. Ackland,
Alexander V. Gourine,
Dmitri A. Rusakov
Affiliations
Olga Kopach
Queen Square Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK; Corresponding author
Sergyi Sylantyev
Queen Square Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK; Rowett Institute, University of Aberdeen, Ashgrove Road West, Aberdeen AB25 2ZD, UK; Corresponding author
Lucie Bard
Queen Square Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
Piotr Michaluk
Queen Square Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK; BRAINCITY, Laboratory of Neurobiology, Nencki Institute of Experimental Biology PAS, 3 Pasteur Street, 02-093 Warsaw, Poland
Janosch P. Heller
Queen Square Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK; School of Biotechnology, Dublin City University, Dublin 9, Ireland
Ana Gutierrez del Arroyo
Translational Medicine and Therapeutics, Queen Mary University of London, Mile End Road, London E1 4NS, UK
Gareth L. Ackland
Translational Medicine and Therapeutics, Queen Mary University of London, Mile End Road, London E1 4NS, UK
Alexander V. Gourine
Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
Dmitri A. Rusakov
Queen Square Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK; Corresponding author
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.
