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dc.contributor.authorHalai, Krishma
dc.date.accessioned2015-09-07T14:46:32Z
dc.date.available2015-09-07T14:46:32Z
dc.date.issued2013
dc.identifier.citationHalai, K. 2013. An investigation into the role of intercellular adhesion molecule-2 in neutrophil extravasation using an in vivo murine model. Queen Mary University of London.en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/8475
dc.descriptionPhDen_US
dc.description.abstractRecruitment of neutrophils into the tissue during inflammation is a crucial component of the immune response. This study aimed to further understand the role of intercellular adhesion molecule-2 (ICAM-2) in this process. Endothelial cell (EC) ICAM-2 has been implicated in neutrophil extravasation however, its precise role in this process is largely unknown. To address this, the current investigation examined the expression and functional role of ICAM-2 in neutrophil-EC interactions in vivo. Analysis of EC ICAM-2 expression was performed in the mouse cremaster muscle using immunofluorescent staining and confocal microscopy. A high EC body expression of ICAM-2 relative to that of EC junctions in post-capillary venules was observed. It was therefore hypothesised that ICAM-2 could potentially be involved in both luminal neutrophil-EC and junctional interactions. This hypothesis was analysed using confocal intravital microscopy (IVM) of cremaster muscles from WT or ICAM-2 KO Lys-eGFP-ki mice (express fluorescent neutrophils) in conjunction with fluorescent labelling of ECs. Neutrophil crawling and transendothelial migration (TEM) dynamics in IL-1β-stimulated post-capillary venules was analysed. A role for ICAM-2 in supporting speed and continuity of crawling and the initiation of TEM was demonstrated. Using functional blocking mAb to MAC-1 in WT and ICAM-2 KOs, the role of ICAM-2 in neutrophil crawling was demonstrated to be governed through a potential interaction with neutrophil MAC-1. It is therefore possible that non-junctional EC ICAM-2 has important roles in regulating neutrophil polarisation during crawling whilst junctional ICAM-2 mediates the opening of EC junctions and/or influencing the site of ‘preferred’ TEM. This study provides the first in vivo evidence for the ability of ICAM-2 to support neutrophil crawling and the initiation of TEM in IL-1β-induced neutrophil extravasation. To extend the above findings in a complex vascular injury model, a cremasteric Shwartzman Reaction, amenable to IVM analysis, was also developed as part of this project.en_US
dc.description.sponsorshipBritish Heart Foundation (BHF)en_US
dc.language.isoenen_US
dc.publisherQueen Mary University of Londonen_US
dc.subjectMedicineen_US
dc.subjectMicrovascular Researchen_US
dc.titleAn investigation into the role of intercellular adhesion molecule-2 in neutrophil extravasation using an in vivo murine modelen_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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    Theses Awarded by Queen Mary University of London

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