dc.contributor.advisor |
Hall, C |
en |
dc.contributor.author |
Keerthisinghe, Pramuk |
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dc.date.accessioned |
2016-11-10T21:16:29Z |
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dc.date.issued |
2015 |
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dc.identifier.uri |
http://hdl.handle.net/2292/31013 |
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dc.description |
Full text is available to authenticated members of The University of Auckland only. |
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dc.description.abstract |
Neutrophils play a crucial role in body’s defence system. Historically, neutrophils were considered to possess little functional heterogeneity. However, it is now becoming apparent that functional neutrophil subsets exists during normal homeostatic condition and even when it is disrupted such as during an infection. Following a severe, systemic infection, neutrophils are consumed in large quantities. Emergency granulopoiesis is the process by which these depleted neutrophil numbers are restored. The evolutionarily conserved immune system and optical transparency of zebrafish have enabled us to live image these emergency granulopoiesis-generated neutrophils and investigate their bactericidal activity. Recent work by the Crosier group has revealed that these emergency granulopoiesis-generated neutrophils possess enhanced bactericidal ROS production when compared to steady state-generated neutrophils. The primary aim of this study was to investigate the mechanism(s) through which emergency granulopoiesis-generated neutrophils possess enhanced bactericidal activity and their effect on larval survival to a subsequent infectious challenge. We also investigated whether these emergency granulopoiesis-generated neutrophils survive to contribute towards the observed enhanced survival when an infection was given several days following the emergency granulopoietic response. Transgenic zebrafish larvae possessing red fluorescent neutrophils were injected with GFP-expressing Salmonella enterica serovar Typhimurium (Sal-GFP) to generate larvae almost entirely populated with emergency granulopoietic neutrophils. Delivering an infection into these larvae enabled us to investigate the behaviour of emergency granulopoiesis-generated neutrophils. This study showed that larvae populated with emergency granulopoiesis-generated neutrophils possessed enhanced survival to a subsequent infection (when compared to larvae populated with steady state-generated neutrophils) through faster clearance of the infection. This elevated anti-bacterial activity demonstrated by larvae populated with emergency granulopoiesis-generated neutrophils was not the result of increased recruitment of neutrophils to the infection site. Further analysis revealed the augmented production of bactericidal ROS by emergency granulopoiesisgenerated neutrophils was NOX-dependent and not the result of macrophage- derived G-CSF a cytokine known to elevate neutrophil ROS production. To the best of our knowledge, this is the first time that functional differences between steady state and emergency granulopoiesisgenerated neutrophils has been examined. These results expand our current understanding of neutrophil heterogeneity and provide new insights into how our innate immune system can be primed for subsequent infectious challenges. |
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dc.publisher |
ResearchSpace@Auckland |
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dc.relation.ispartof |
Masters Thesis - University of Auckland |
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dc.relation.isreferencedby |
UoA99264894413302091 |
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dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
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dc.rights |
Restricted Item. Available to authenticated members of The University of Auckland. |
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dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
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dc.rights.uri |
http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ |
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dc.title |
Investigating the functional difference between neutrophils generated by emergency versus steady state granulopoiesis |
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dc.type |
Thesis |
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thesis.degree.discipline |
Biomedical Science |
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thesis.degree.grantor |
The University of Auckland |
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thesis.degree.level |
Masters |
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dc.rights.holder |
Copyright: The author |
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pubs.elements-id |
545800 |
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pubs.org-id |
Medical and Health Sciences |
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pubs.org-id |
Medical Sciences |
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pubs.org-id |
Molecular Medicine |
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pubs.record-created-at-source-date |
2016-11-11 |
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dc.identifier.wikidata |
Q112909426 |
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