Abstract：
Neutrophils collectively migrate to sites of injury and infection. How these swarms are coordinated to ensure the proper level of recruitment is unknown. Using an ex vivo model of infection, we show that human neutrophil swarming is organized by multiple pulsatile chemoattractant waves. These waves propagate through active relay in which stimulated neutrophils trigger their neighbors to release additional swarming cues. Unlike canonical active relays, we find these waves to be self-terminating, limiting the spatial range of cell recruitment. We identify an NADPH-oxidase-based negative feedback loop that is needed for this self-terminating behavior. We observe near-constant levels of neutrophil recruitment over a wide range of starting conditions, revealing surprising robustness in the swarming process. This homeostatic control is achieved by larger and more numerous swarming waves at lower cell densities. We link defective wave termination to a broken recruitment homeostat in the context of human chronic granulomatous disease.
摘要：
中性粒细胞共同迁移到损伤和感染部位。如何协调这些群体以确保适当的招聘水平是未知的。使用离体感染模型，我们表明，人类中性粒细胞群聚是由多个脉动化学引诱波组织的。这些波通过主动中继传播，受刺激的嗜中性粒细胞触发其邻居释放额外的蜂群线索。与规范的有源继电器不同，我们发现这些波是自我终止的，限制了细胞募集的空间范围。我们确定了这种自我终止行为所需的基于NADPH氧化酶的负反馈回路。我们观察到中性粒细胞募集在广泛的起始条件下接近恒定的水平，在蜂拥而至的过程中揭示了令人惊讶的稳健性。这种稳态控制是通过在较低细胞密度下更大和更多的蜂群波来实现的。在人类慢性肉芽肿疾病的背景下，我们将有缺陷的波终止与破裂的募集稳态仪联系起来。
