Novel roles of the L-selection receptor on lymphocytes in cell division and signal transduction

Leukocyte extravasation is a regulated mechanism involving the initial contact, adhesion, and transmigration of leukocytes through layers of endothelial cells into the surrounding tissue. L-selectin is the peripheral lymph node homing receptor mediating the initial interaction and weak adhesion between lymphocytes and endothelial cells. This thesis presents two non-traditional roles of L-selectin-involvement in cell division and signaling.Cytokinesis is the last phase of mitosis in which the plasma membrane invagination occurs between the newly formed daughter cells. L-selectin concentrates along the cleavage furrow of dividing Daudi cells. Arresting cells after completing mitosis results in detectable shed L-selectin in the culture supernatant. In contrast, no soluble L-selectin is detected after arresting cells in the G$ sb2$ phase. This suggests that the relocation and shedding of the L-selectin receptor is involved in cytokinesis of Daudi cells.In addition, calcium mobilization from internal stores is induced using the L-selectin monoclonal antibody, FMC46, on normal peripheral blood mononuclear cells (PBMCs) and Daudi cells. Priming of PBMCs with FMC46 before Pokeweed mitogen (PWM) stimulation increased aggregation and proliferation at lower doses of PWM compared to lymphocytes stimulated with PWM alone. These data provide evidence for direct alteration of lymphocyte activation status after ligation of a specific L-selectin epitope. The physiological role of L-selectin-mediated signaling may be important in the priming of lymphocytes during extravasation such that lymphocytes are more responsive to antigenic stimulation after completing transmigration