Direct In Vivo Manipulation and Imaging of Calcium Transients in Neutrophils Identify a Critical Role for Leading-Edge Calcium Flux.
Abstract
Calcium signaling has long been associated with key events of immunity, including
chemotaxis, phagocytosis, and activation. However, imaging and manipulation of calcium
flux in motile immune cells in live animals remain challenging. Using light-sheet
microscopy for in vivo calcium imaging in zebrafish, we observe characteristic patterns
of calcium flux triggered by distinct events, including phagocytosis of pathogenic
bacteria and migration of neutrophils toward inflammatory stimuli. In contrast to
findings from ex vivo studies, we observe enriched calcium influx at the leading edge
of migrating neutrophils. To directly manipulate calcium dynamics in vivo, we have
developed transgenic lines with cell-specific expression of the mammalian TRPV1 channel,
enabling ligand-gated, reversible, and spatiotemporal control of calcium influx. We
find that controlled calcium influx can function to help define the neutrophil's leading
edge. Cell-specific TRPV1 expression may have broad utility for precise control of
calcium dynamics in other immune cell types and organisms.
Type
Journal articleSubject
AnimalsAnimals, Genetically Modified
Calcium
Calcium Signaling
Chemotaxis
Microscopy, Fluorescence
Neutrophils
Rats
TRPV Cation Channels
Zebrafish
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https://hdl.handle.net/10161/12637Published Version (Please cite this version)
10.1016/j.celrep.2015.11.010Publication Info
Tobin, DM (2015). Direct In Vivo Manipulation and Imaging of Calcium Transients in Neutrophils Identify
a Critical Role for Leading-Edge Calcium Flux. Cell Rep, 13(10). pp. 2107-2117. 10.1016/j.celrep.2015.11.010. Retrieved from https://hdl.handle.net/10161/12637.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
David M. Tobin
Associate Professor of Molecular Genetics and Microbiology
Tuberculosis: Mycobacterial Pathogenesis and Host Susceptibility
Tuberculosis kills 1.5 million people annually. Our laboratory aims to understand
the intricate interplay between mycobacteria and their hosts using a combination of
model organism genetics, human genetics, pharmacology and high-resolution microscopy.
By identifying key pathways utilized by the infecting bacteria and the host innate
immune system, we hope to discover new therapeutic targets and interventi

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