BioMEMS Resource Center, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospital for Children, Charlestown, MA, 02129, USA.
Lab Chip. 2014 Mar 7;14(5):972-978. doi: 10.1039/c3lc50959a.
Neutrophils are the most abundant type of white blood cells in the circulation, protecting the body against pathogens and responding early to inflammation. Although we understand how neutrophils respond to individual stimuli, we know less about how they prioritize between competing signals or respond to combinational signals. This situation is due in part to the lack of adequate experimental systems to provide signals in controlled spatial and temporal fashion. To address these limitations, we designed a platform for generating on-demand, competing chemical gradients and for monitoring neutrophil migration. On this platform, we implemented forty-eight assays generating independent gradients and employed synchronized valves to control the timing of these gradients. We observed faster activation of neutrophils in response to fMLP than to LTB4 and unveiled for the first time a potentiating effect for fMLP during migration towards LTB4. Our observations, enabled by the new tools, challenge the current paradigm of inhibitory competition between distinct chemoattractant gradients and suggest that human neutrophils are capable of complex integration of chemical signals in their environment.
中性粒细胞是循环中数量最多的白细胞类型，可保护身体免受病原体侵害，并对炎症做出早期反应。虽然我们了解中性粒细胞如何对单个刺激做出反应，但对于它们如何在竞争信号之间进行优先级排序或对组合信号做出反应知之甚少。这种情况部分是由于缺乏足够的实验系统来以受控的时空方式提供信号。为了解决这些限制，我们设计了一个平台，用于生成按需、竞争的化学梯度，并用于监测中性粒细胞的迁移。在这个平台上，我们实现了四十八种独立梯度的检测，并采用同步阀来控制这些梯度的时间。我们观察到，与 LTB4 相比，中性粒细胞对 fMLP 的反应更快，并首次揭示了在向 LTB4 迁移过程中 fMLP 的增强作用。我们的观察结果得益于新工具的应用，挑战了不同趋化因子梯度之间抑制竞争的现有范式，并表明人类中性粒细胞能够在其环境中对化学信号进行复杂的整合。
