dc.contributor.author | Halai, Krishma | |
dc.date.accessioned | 2015-09-07T14:46:32Z | |
dc.date.available | 2015-09-07T14:46:32Z | |
dc.date.issued | 2013 | |
dc.identifier.citation | Halai, 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.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/8475 | |
dc.description | PhD | en_US |
dc.description.abstract | Recruitment 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.sponsorship | British Heart Foundation (BHF) | |
dc.language.iso | en | en_US |
dc.publisher | Queen Mary University of London | |
dc.subject | Electronic Engineering | en_US |
dc.subject | Computer Science | en_US |
dc.title | An investigation into the role of intercellular adhesion molecule-2 in neutrophil extravasation using an in vivo murine model | en_US |
dc.type | Thesis | en_US |
dc.rights.holder | The 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 | |