Increased expression of Lewis X and Y antigens on the cell surface and FUT 4 mRNA during granzyme B-induced Jurkat cell apoptosis

Abstract

Cytotoxic T cells and natural killer cells play key roles in cell-mediated cytotoxicity and can induce apoptosis in virus-infected and malignant cells by releasing cytotoxic granules. In the current study, apoptosis was induced in Jurkat cells, a human T cell line, by delivering granzyme B into the cells using BioPORTER®, a cationic lipid formulation. During granzyme B-induced apoptosis, there was an increase in the cell surface expression of Lewis X and Y antigens. To clarify the roles of initiator and executioner caspases in the expression of Lewis X and Y antigens, we treated Jurkat cells with granzyme B in the presence of caspase 3, 8, and 9 inhibitors. The results indicated that delivery of granzyme B into Jurkat cells induces apoptosis by activating caspase 3 and that caspase 3 but not caspase 8 and 9 plays a key role in enhancing the expression of Lewis X and Y antigens. Realtime PCR revealed that expression of the mRNAs for α1,3-fucosyltransferases FUT4 was increased at 3 h during granzyme B-induced apoptosis, while FUT9 mRNA expression gradually increased after 12 h. This increased expression of FUT4 mRNA occurred downstream of caspase 3 activation and resulted in the increased cell surface expression of Lewis X and Y antigens. © 2007 Pharmaceutical Society of Japan.