Mechanical deformation induces depolarization of neutrophils
American Association for the Advancement of Science
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Ekpenyong, A., Toepfner, N., Fiddler, C., Herbig, M., Li, W., Cojoc, G., Summers, C., et al. (2017). Mechanical deformation induces depolarization of neutrophils. Science Advances, 3 (6. e1602536)https://doi.org/10.1126/sciadv.1602536
The transition of neutrophils from a resting state to a primed state is an essential requirement for their function as competent immune cells. This transition can be caused not only by chemical signals but also by mechanical perturbation. After cessation of either, these cells gradually revert to a quiescent state over 40 to 120 min. We use two biophysical tools, an optical stretcher and a novel microcirculation mimetic, to effect physiologically relevant mechanical deformations of single nonadherent human neutrophils. We establish quantitative morphological analysis and mechanical phenotyping as label-free markers of neutrophil priming. We show that continued mechanical deformation of primed cells can cause active depolarization, which occurs two orders of magnitude faster than by spontaneous depriming. This work provides a cellular-level mechanism that potentially explains recent clinical studies demonstrating the potential importance, and physiological role, of neutrophil depriming in vivo and the pathophysiological implications when this deactivation is impaired, especially in disorders such as acute lung injury.
leukocyte, neutrophil, acute lung injury, cell mechanics, chronic occlusive pulmonary disorder, de-priming, inflammation, microfluidics, optical stretcher, priming
We acknowledge financial support by the Cambridge Commonwealth Trust (to A.E.E.), the European Research Council (Starting Grant “Light Touch” to J.G.), and the National Institute for Health Research Cambridge Biomedical Research Centre (to E.R.C.). C.S. is a Wellcome Trust Postdoctoral Clinical Research Fellow (101692MA), and C.F. is a Medical Research Council Clinical Training Fellow.
Wellcome Trust (101692/Z/13/Z)
External DOI: https://doi.org/10.1126/sciadv.1602536
This record's URL: https://www.repository.cam.ac.uk/handle/1810/265212
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