dc.contributor.advisor McIntire, Larry V. Jones, David Alan 2009-06-04T00:12:58Z 2009-06-04T00:12:58Z 1994 https://hdl.handle.net/1911/16745 Leukocyte adhesion to the endothelial cells lining blood vessel walls is a central event in the body's response to injury or infection. These interactions take place in the flowing bloodstream, and previous work has shown that fluid flow effects greatly influence the function of the adhesion receptors involved. In these studies, we use a parallel-plate flow chamber and videomicroscopy to quantitate leukocyte adhesion under flow conditions in vitro. First, we report studies of neutrophil adhesion to histamine-stimulated human umbilical vein endothelial cells (HUVECs). Most neutrophils roll along the HUVECs under these conditions, and a few adhere firmly. The rolling is mediated by P-selectin while the firm adhesion is mediated by $\beta\sb2$ integrins binding to ICAM-1, and we quantitate these interactions to generate data useful in understanding selectin-mediated rolling and integrin-mediated firm adhesion. Next, we report studies of T lymphocyte adhesion to HUVECs stimulated for 24 hours with interleukin-l (IL-1). Firm adhesion of T cells in this system is mediated by both ICAM-1/$\alpha\sb{L}\beta\sb2$ integrin and VCAM-1/$\alpha\sb4\beta\sb1$ integrin interactions, and we find that initial adhesion and rolling are mediated by a third pathway which does not appear to involve any of the previously characterized adhesion molecules. To investigate the molecular constituents of this pathway, we use a monoclonal antibody approach based on the observation that HUVECs stimulated with both IL-1 and IL-4 do not support any adhesion of T cells under flow conditions even though expression of the known endothelial cell adhesion receptors is similar to expression on IL-1-stimulated HUVECs. This approach has not yet been successful, and we also report results of preliminary experiments related to possible alternative approaches. 165 p. application/pdf eng Chemical engineeringCell biologyBiologyEngineering Leukocyte adhesion to endothelial cells under flow conditions Thesis Text Biology Natural Sciences Rice University Doctoral Doctor of Philosophy Jones, David Alan. "Leukocyte adhesion to endothelial cells under flow conditions." (1994) Diss., Rice University. https://hdl.handle.net/1911/16745.
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