Increased expression of Lewis X and Y antigens on the cell surface and FUT 4 mRNA during granzyme B-induced Jurkat cell apoptosis.
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. Real-time PCR revealed that expression of the mRNAs for alpha1,3-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.
Azuma
Yutaro
Y
Department of Clinical Chemistry, School of Pharmaceutical Sciences, Toho University, Japan. yutaro@phar.toho-u.ac.jp
Kurusu
Yoshikazu
Y
Sato
Hirotaka
H
Higai
Koji
K
Matsumoto
Kojiro
K
D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005647:Fucosyltransferases / Q000378:metabolism*; D053804:Granzymes / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D007983:Lewis Blood Group Antigens / Q000378:metabolism*; D016256:Lewis X Antigen / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D061945:Caspase Inhibitors; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; C094162:Lewis Y antigen; D012333:RNA, Messenger; C066693:FUT4 protein, human; D005647:Fucosyltransferases; D053804:Granzymes