Kopach Olga, Sylantyev Sergyi, Bard Lucie, Michaluk Piotr, Heller Janosch P, Gutierrez Del Arroyo Ana, Ackland Gareth L, Gourine Alexander V, Rusakov Dmitri A
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.
iScience. 2023 Jun 28;26(7):107236. doi: 10.1016/j.isci.2023.107236. eCollection 2023 Jul 21.
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.
中性粒细胞是对急性炎症和适应性免疫反应至关重要的白细胞。它们的集群模式行为由多个细胞级联控制，这些级联涉及多种信号分子的钙依赖性释放。先前的研究报道中性粒细胞表达谷氨酸受体并能释放谷氨酸，但中性粒细胞之间直接通讯的证据一直难以捉摸。在这里，我们以膜片钳全细胞模式对悬浮培养的人中性粒细胞进行研究，发现刺激一个中性粒细胞诱导的钙动员可触发相邻中性粒细胞中由N-甲基-D-天冬氨酸（NMDA）受体驱动的膜电流和钙信号。我们采用基于酶的成像测定法实时成像由相邻中性粒细胞释放的谷氨酸诱导的中性粒细胞谷氨酸释放。这些观察结果为中性粒细胞间的正反馈通讯提供了直接证据，这可能有助于调节中性粒细胞群体行为的机制。
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