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dc.contributor.authorLeese, Andrew John
dc.date.accessioned2016-06-14T11:01:58Z
dc.date.available2016-06-14T11:01:58Z
dc.date.issued2016-11-06
dc.date.submitted2016-06-14T09:39:41.903Z
dc.identifier.citationLeese, A.J. 2016 : Investigating the expression and function of neutrophil elastase in murine monocyte migration in vivo, Queen Mary University of London.en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/12853
dc.descriptionPhDen_US
dc.description.abstractMonocytes comprise a key component of the innate immune system. Their excessive and/or prolonged recruitment and/or activation can however be harmful and has been associated with the pathogenesis of numerous inflammatory disorders, most notably atherosclerosis. Consequently there is much interest in deciphering the mechanisms by which monocytes migrate into sites of inflammation. In this context, whilst many studies have investigated the roles of adhesion molecules and chemokine receptors, very little attention has been placed on the potential involvement of proteases. To help address this point, and considering cigarette smoke-induced recruitment of monocytes to the lung is impaired in mice deficient in neutrophil elastase (NE-/-), we sought to further investigate the role of NE, a serine protease, in monocyte migration. To achieve this we successfully crossed CX3CR1-eGFP-knock-in mice, which exhibit fluorescently labelled monocytes, with NE-/- mice. By comparing NE-/- and NE+/+ littermates we demonstrated, for the first time, NE expression in murine monocytes. Peritonitis, ear, and cremaster muscle models of inflammation were subsequently employed to assess the involvement of NE in monocyte recruitment. In CCL2-induced peritonitis, a predominantly monocyte-driven inflammatory model, monocyte infiltration was significantly reduced after 16 hours in NE-/- mice compared to NE+/+ controls. Monocyte transmigration was also defective in the ears (though interestingly not the cremaster muscles) of NE-/- mice stimulated with CCL2, with the majority of monocytes seemingly unable to penetrate the venular endothelium. Furthermore, immunostaining revealed transmigrating monocytes were depleted of their intracellular NE stores. Taken together, it appears the release of NE by monocytes promotes their transmigration in response to CCL2, identifying NE as a potential therapeutic target for monocyte-driven pathologies.
dc.language.isoenen_US
dc.publisherQueen Mary University of Londonen_US
dc.subjectMedicineen_US
dc.subjectMonocytesen_US
dc.subjectatherosclerosisen_US
dc.subjectneutrophil elastaseen_US
dc.subjectimmune system.en_US
dc.titleInvestigating the expression and function of neutrophil elastase in murine monocyte migration in vivoen_US
dc.typeThesisen_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author


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