Mechanical deformation induces depolarization of neutrophils

Andrew Ekpenyong, Nicole Toepfner, Christine Fiddler, Maik Herbig, Wenhong Li, Gheorghe Cojoc, Charlotte Summers, Jochen Guck, Edwin R. Chilvers

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere1602536
JournalScience advances
Volume3
Issue number6
DOIs
StatePublished - Jun 1 2017

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Ekpenyong, A., Toepfner, N., Fiddler, C., Herbig, M., Li, W., Cojoc, G., Summers, C., Guck, J., & Chilvers, E. R. (2017). Mechanical deformation induces depolarization of neutrophils. Science advances, 3(6), [e1602536]. https://doi.org/10.1126/sciadv.1602536