Interaction with an endothelial lumen increases neutrophil lifetime and motility in response to P aeruginosa.

Blood
Laurel E HindAnna Huttenlocher

Abstract

Neutrophil infiltration into tissues is essential for host defense and pathogen clearance. Although many of the signaling pathways involved in the transendothelial migration of neutrophils are known, the role of the endothelium in regulating neutrophil behavior in response to infection within interstitial tissues remains unclear. Here we developed a microscale 3-dimensional (3D) model that incorporates an endothelial lumen, a 3D extracellular matrix, and an intact bacterial source to model the host microenvironment. Using this system, we show that an endothelial lumen significantly increased neutrophil migration toward a source of Pseudomonas aeruginosa Surprisingly, we found neutrophils, which were thought to be short-lived cells in vitro, migrate for up to 24 hours in 3D in the presence of an endothelial lumen and bacteria. In addition, we found that endothelial cells secrete inflammatory mediators induced by the presence of P aeruginosa, including granulocyte-macrophage colony-stimulating factor (GM-CSF), a known promoter of neutrophil survival, and interleukin (IL)-6, a proinflammatory cytokine. We found that pretreatment of neutrophils with a blocking antibody against the IL-6 receptor significantly reduced neutrophil migr...Continue Reading

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Citations

Oct 27, 2018·Blood·Ricardo Grieshaber-Bouyer, Peter A Nigrovic
Aug 8, 2020·Chemical Society Reviews·María Virumbrales-MuñozDavid J Beebe
Sep 8, 2020·Advanced Healthcare Materials·Joe Tien, Yoseph W Dance
Nov 15, 2019·Journal of Cell Science·Taylor J SchoenAnna Huttenlocher
Sep 29, 2020·Frontiers in Bioengineering and Biotechnology·Carlotta MondadoriChiara Arrigoni
Oct 10, 2020·Integrative Biology : Quantitative Biosciences From Nano to Macro·Sheena C KerrDavid J Beebe
Apr 20, 2021·Cellular and Molecular Bioengineering·Laurel E HindAnna Huttenlocher
May 15, 2021·Frontiers in Immunology·Isaac M RichardsonLaurel E Hind

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