Whole blood human neutrophil trafficking in a microfluidic model of infection and inflammation.
Whole blood human neutrophil trafficking in a microfluidic model of infection and inflammation.
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DOI：
10.1039/c5lc00245a
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发表时间：
2015-06-21
期刊：
影响因子：
6.1
通讯作者：
Irimia D
中科院分区：
文献类型：
--
作者：
Hamza B;Irimia D
对伤口和感染的适当炎症反应需要足够数量的中性粒细胞到达损伤部位。中性粒细胞募集不足和过度都可能是有害的，有利于微生物的全身传播或引发严重的组织损伤。尽管其在健康和疾病中的重要性，但中性粒细胞通过组织的运输仍然难以控制，并且对其调节机制的理解也不够。这些机制也很复杂，难以使用传统的体内模型分离。在这里，我们设计了一个组织感染/炎症的微流体模型，其中人类嗜中性粒细胞从全血的液滴大小的样品中出现，并在此与含有化学引诱剂和微生物样颗粒的微室之间显示双向交通。两个几何屏障限制红细胞从血液进入微室，并模拟将血液中的细胞与组织中的细胞分离的内皮屏障的机械功能。我们发现，在化学引诱物的存在下，通过逆行性离开腔室的中性粒细胞的数量与通过趋化性招募的中性粒细胞处于动态平衡。我们还发现，在存在微生物样颗粒的情况下，被困在腔室中的中性粒细胞的数量与颗粒的数量成正比。总之，迁移、反向迁移和捕获过程之间的动态平衡决定了一个部位中性粒细胞的最佳数量。这些中性粒细胞不断更新并对微生物的数量做出反应。使用这种感染-炎症-芯片模型的进一步研究可以帮助研究炎症消退的过程。新的体外实验工具也可能最终有助于测试新的治疗策略，以限制慢性炎症期间组织中的中性粒细胞积聚，而不会增加感染的风险。
Appropriate inflammatory responses to wounds and infections require adequate numbers of neutrophils arriving at injury sites. Both insufficient and excessive neutrophil recruitment can be detrimental, favouring systemic spread of microbes or triggering severe tissue damage. Despite its importance in health and disease, the trafficking of neutrophils through tissues remains difficult to control and the mechanisms regulating it are insufficiently understood. These mechanisms are also complex and difficult to isolate using traditional in vivo models. Here we designed a microfluidic model of tissue infection/inflammation, in which human neutrophils emerge from a droplet-size samples of whole blood and display bi-directional traffic between this and micro-chambers containing chemoattractant and microbe-like particles. Two geometrical barriers restrict the entrance of red blood cells from the blood to the micro-chambers and simulate the mechanical function of the endothelial barrier separating the cells in blood from cells in tissues. We found that in the presence of chemoattractant, the number of neutrophils departing the chambers by retrotaxis is in dynamic equilibrium with the neutrophils recruited by chemotaxis. We also found that in the presence of microbe-like particles, the number of neutrophils trapped in the chambers is proportional to the number of particles. Together, the dynamic equilibrium between migration, reversed-migration and trapping processes determine the optimal number of neutrophils at a site. These neutrophils are continuously refreshed and responsive to the number of microbes. Further studies using this infection-inflammation-on-a-chip-model could help study the processes of inflammation resolution. The new in vitro experimental tools may also eventually help testing new therapeutic strategies to limit neutrophil accumulation in tissues during chronic inflammation, without increasing the risk for infections.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
82.9
作者：
Phillipson M;Kubes P
通讯作者：
Kubes P
感染期间淋巴结中中性粒细胞迁移的动态。
影响因子：
32.4
作者：
Chtanova, Tatyana;Schaeffer, Marie;Han, Seong-Ji;van Dooren, Giel G.;Nollmann, Marcelo;Herzmark, Paul;Chan, Shiao Wei;Satija, Harshita;Camfield, Kristin;Aaron, Holly;Striepen, Boris;Robey, Ellen A.
通讯作者：
Robey, Ellen A.
影响因子：
20.3
作者：
Gordy, Claire;Pua, Heather;He, You-Wen
通讯作者：
He, You-Wen
影响因子：
6.4
作者：
Shannon JG;Hasenkrug AM;Dorward DW;Nair V;Carmody AB;Hinnebusch BJ
通讯作者：
Hinnebusch BJ