Ligation of the LEU-13 cell surface molecule functionally downregulates the l-selectin homing receptor

The L-selectin adhesion molecule initiates lymphocyte extravasation into secondary lymphoid tissues and at sites of inflammation. In this report we demonstrate a novel level of regulation of L-selectin-mediated adhesion events which involves the Leu-13 surface protein. Leu-13 is a member of a signal transduction complex that includes TAPA-1 (CD81) on B and T cells as well as CD19 and CD21 on B lymphocytes. In the present study, antibody-induced cross-linking of Leu-13 triggered rapid (i.e., within 1 h) downregulation of L-selectin surface expression by normal and malignant B and T lymphocytes. In contrast, anti-Leu-13 had little to no effect on the expression of other lymphocyte surface molecules including LFA-1, ICAM-1, CD44, LFA-3, CD3, CD4, CD5, CD8, or CD45. Leu-13 ligation also inhibited L-selectin-mediated binding of lymphocytes to the soluble carbohydrate PPME as well as to vascular endothelial cells. Finally, anti-Leu-13 monoclonal antibodies were shown to act via a tyrosine-kinase dependent pathway to initiate L-selectin shedding from the lymphocyte cell surface. These data, together with evidence from previous reports indicating that anti-Leu-13 antibodies deliver potent antiproliferative signals to normal and malignant lymphocytes, suggest that anti-Leu- 13-induced downregulation of L-selectin represents a novel approach toward interfering with L-selectin-mediated lymphocyte homing in pathological disorders including chronic inflammation and metastasis.