<p>Cell-cell adhesion is an important and an initiating event in thrombosis, inflammation and metastasis. Recent data suggest that these adhesion events are mediated by cell adhesion receptors and/or ligands present on blood cells, the endothelium and the basement membrane underlying the endothelium. This thesis hypothesizes that endogenous lipoxygenase metabolites regulate blood cell-vessel wall interactions. The following data, as presented in this thesis, support this hypothesis. First, the intracellular level of 13-HODE in endothelial cells, inversely correlated with platelet, tumor cell and leukocyte adhesion. Second, intracellular 13-HODE levels and/or 13-HODE:HETE ratios in blood cells and in tumor cells also inversely correlated with cell adhesivity. Third, the level of 13-HODE in basement membranes and in artificial grafts, inversely correlated with platelet adhesion. Fourth, 13-HODE co-localized with the vitronectin receptor (VnR) in resting endothelial cells. Following stimulation, 13-HODE and the VnR dissociated, and the VnR relocated to the periphery surface of the endothelial cell. Fifth, the increased peripheral expression of the VnR on stimulated endothelial cells mediated platelet adhesion. Finally modulation of the lipoxygenase pathway markedly influenced experimentally-induced thrombosis. In summary, there is an abundance of data presented in this thesis which suggest that monohydroxy lipoxygenase metabolites regulate blood cell-vessel wall adhesion. This regulation appears to be a result of lipoxygenase metabolites influencing adhesion receptor/ligand recognition. Therefore, it is a reasonable expectation that agents which modulate the lipoxygenase pathway may also be useful in the prevention and treatment of thrombosis, inflammation, and metastasis.</p> / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/8409 |
| Date | 04 1900 |
| Creators | Haas, Thomas A. |
| Contributors | Buchanan, M.R., Medical Sciences |
| Source Sets | McMaster University |
| Detected Language | English |
| Type | thesis |
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