| High endothelial venule (HEV) cells are specialized endothelial cells found in post capillary venules within the paracortical areas of secondary lymphoid tissues. These cuboidal-shaped endothelial cells are most prominently known for their role in promoting naive lymphocyte migration from the blood into these peripheral lymphoid tissues (2). However, we have demonstrated that HEV cells also perform the additional function of recognizing and phagocytosing apoptotic leukocytes (3), (Chapter 3).; We have determined that the order in which four types of leukocytes obtain apoptotic characteristics was dependent on both the cell type and the method of inducing apoptosis (Chapter 4). Secondly, WEHI-231 cells that have been induced to undergo apoptosis by two different methods have two different orders in which they acquire apoptotic membrane and nuclear changes (Chapter 4).; Removal of apoptotic cells is pivotal for tissue protection against toxic cellular debris, such as noxious enzymes and auto antigens. We developed a flow cytometry-based assay to quantitate HEV cell phagocytosis (10), (Chapter 2). Our assay differentiates between HEV cells with internalized cells versus cells that are merely bound to the HEV cells' surface. In Chapter 5, we examined the phagocytic receptors utilized by mHEV cells to ingest apoptotic leukocytes and correlated receptor usage with acquisition of apoptotic characteristics by apoptotic leukocytes as determined in Chapter 4. Using our phagocytic assay (Chapter 2), we ascertained that the mHEV cells utilized fucoidin and mannan-specific lectin receptors to internalize apoptotic cells, prior to apoptotic cell membrane and nuclear changes that were examined.; The results contained herein confirms that mHEV cells are able to phagocytose apoptotic cells via fucoidin/mannan-specific lectin receptors while promoting lymphocyte transendothelial migration. This suggests that in vivo , HEV cells have the ability to regulate lymphocyte trafficking successfully and maintain tissue homeostasis in the surrounding microvasculature and lymphoid tissues. Moreover, these results imply that HEV cells remove apoptotic cells to insure that only viable lymphocytes migrate into lymphoid tissues to encounter sequestered antigen and become stimulated to confront pathological agents at sites of infection and inflammation. (Abstract shortened by UMI.)... |
