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Neutrophil trafficking on-a-chip: an in vitro, organotypic model for investigating neutrophil priming, extravasation, and migration with spatiotemporal control

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Abstract

Neutrophil trafficking is essential for a strong and productive immune response to infection and injury. During acute inflammation, signals from resident immune cells, fibroblasts, and the endothelium help to prime, attract, and activate circulating neutrophils at sites of inflammation. Due to current limitations with in vitro and animal models, our understanding of these events is incomplete. In this paper, we describe a microfluidic technology which incorporates a lumen-based vascular component with a high degree of spatiotemporal control to facilitate the study of neutrophil trafficking using primary human cells. The improved spatiotemporal control allows functional selection of neutrophils based on their migratory capacity. We use this technology to investigate neutrophil–endothelial interactions and find that these interactions are necessary for robust neutrophil chemotaxis to interleukin-8 (IL-8) and priming of the neutrophils. In agreement with previous studies, we observed that transendothelial migration (TEM) is required for neutrophils to enter a primed phenotypic state. TEM neutrophils not only produce a significantly higher amount of reactive oxygen species (ROS) when treated with PMA, but also upregulate genes involved in ROS production (CYBB, NCF1, NFKB1, NFKBIA), cell adhesion (CEACAM-8, ITGAM), and chemokine receptors (CXCR2, TNFRSF1A). These results suggest that neutrophil–endothelial interactions are crucial to neutrophil chemotaxis and ROS generation.

Graphical abstract: Neutrophil trafficking on-a-chip: an in vitro, organotypic model for investigating neutrophil priming, extravasation, and migration with spatiotemporal control

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Publication details

The article was received on 13 Jun 2019, accepted on 15 Sep 2019 and first published on 18 Sep 2019


Article type: Paper
DOI: 10.1039/C9LC00562E
Lab Chip, 2019, Advance Article

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    Neutrophil trafficking on-a-chip: an in vitro, organotypic model for investigating neutrophil priming, extravasation, and migration with spatiotemporal control

    P. H. McMinn, L. E. Hind, A. Huttenlocher and D. J. Beebe, Lab Chip, 2019, Advance Article , DOI: 10.1039/C9LC00562E

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