Human neutrophil elastase phenotyping: classifying neutrophils by function with novel imaging agents
dc.contributor.advisor
Dhaliwal, Kanwaldeep
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dc.contributor.advisor
Bradley, Mark
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dc.contributor.advisor
Dweck, Marc
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dc.contributor.author
Campbell, Thane Allardyce
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dc.contributor.sponsor
Engineering and Physical Sciences Research Council (EPSRC)
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dc.date.accessioned
2020-01-30T12:28:17Z
dc.date.available
2020-01-30T12:28:17Z
dc.date.issued
2020-01-27
dc.description.abstract
This thesis describes approaches taken to classify the functionally diverse neutrophil
by its different functions in a live-cell imaging tool. Human neutrophil elastase
(HNE) cleaves over 30 substrates, its release is controlled with varying extents of
degranulation and its activity is subject to complex modulation. HNE regulation is
necessary for the maintenance of health via HNE’s multiplicity of functions.
Although neutrophils are routinely quantified in assessments of chronic
inflammation, we do not have a clinically translatable, integrated tool for measuring
HNE in human tissues. Two novel probes have been characterised and multiplexed
to form the basis of an imaging technique for understanding the functional
implications of neutrophil activity in human tissues, in real-time. Neutrophil
Activation Probe (NAP) and VE200 are novel probes for HNE activity and presence.
These probes are characterised in vitro as sensitive and HNE-specific imaging agents
for live-cell imaging and image cytometry.
Multiplexed NAP and HNE are detect neutrophil activation, apoptosis and necrosis.
These imaging agents can inform deep profiling techniques to separate neutrophils
into untreated, primed, activated and primed-activated states and endogenous vs.
exogenous stimulus sub-states. Finally, sections of adenocarcinomatous human lung
and whole human lungs, ventilated ex vivo, demonstrate the applicability of HNEbased,
multiparametric profiling and neutrophil activation detection to clinically
relevant platforms.
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dc.identifier.uri
https://hdl.handle.net/1842/36712
dc.identifier.uri
http://dx.doi.org/10.7488/era/19
dc.language.iso
en
dc.publisher
The University of Edinburgh
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dc.relation.hasversion
Birch, G., Campbell, T., Bradley, M. and Dhaliwal, K., 2019. Optical molecular imaging of inflammatory cells in interventional medicine-an emerging strategy. Frontiers in Oncology, 9, p.882.
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dc.subject
neutrophil
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dc.subject
neutrophil elastase
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dc.subject
probe
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dc.subject
fibred confocal endomicroscopy
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dc.subject
machine learning
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dc.title
Human neutrophil elastase phenotyping: classifying neutrophils by function with novel imaging agents
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dc.type
Thesis or Dissertation
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dc.type.qualificationlevel
Doctoral
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dc.type.qualificationname
PhD Doctor of Philosophy
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