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Title: LYVE-1 and the response of lymphatic vessel endothelium to inflammation
Author: Johnson, Louise Anne
ISNI:       0000 0001 3591 2411
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2005
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The lymphatic system provides a conduit for the delivery of antigen-presenting cells from peripheral tissues to draining lymph nodes, both constitutively and during inflammation, when a dramatic increase in the number of trafficking events occurs. This thesis is concerned with the role played by the lymphatic endothelium under pro-inflammatory conditions and the mechanisms regulating entry of leukocytes into the lymphatic capillaries. Monoclonal antibodies against the lymphatic vessel endothelial-specific receptor for hyaluronan, LYVE-1, were raised in rat against the mouse orthologue, for use both as a marker for lymphatics in mouse tissue and to investigate the physiological role of this protein. LYVE-1 was found to be dramatically and specifically down-regulated by TNFa and TNFp, by rapid internalisation and transcriptional down-regulation in primary lymphatic endothelial cells. A significant reduction in LYVE-1 expression was also recorded in intact lymphatic vessels in response to TNFa and in an allergen-induced mouse model of skin inflammation. Furthermore, lymphatic endothelial cells were found to respond to this pro-inflammatory cytokine by instigating a distinct expression programme characterised by up-regulation of the key leukocyte adhesion receptors VCAM-1, ICAM-1 and E-selectin; chemokines and other potential regulators of leukocyte entry. Moreover, the major components of this programme were confirmed in dermal lymphatic vessels in the allergen-induced mouse model of skin inflammation, simultaneous with the down-modulation of LYVE-1 and lymphatic accumulation of migrating leukocytes. The results described in this thesis provide the first evidence that lymphatic endothelial cells play an active role in inflammation. In addition these data indicate that the lymphatic and blood vascular systems share components of the same address code for specific vascular targeting.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral