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

Biol Pharm Bull. 2007 Apr;30(4):655-60. doi: 10.1248/bpb.30.655.

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. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspase Inhibitors
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Fucosyltransferases / metabolism*
  • Granzymes / pharmacology*
  • Humans
  • Jurkat Cells
  • Lewis Blood Group Antigens / metabolism*
  • Lewis X Antigen / metabolism*
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Time Factors

Substances

  • Caspase Inhibitors
  • Lewis Blood Group Antigens
  • Lewis X Antigen
  • Lewis Y antigen
  • RNA, Messenger
  • FUT4 protein, human
  • Fucosyltransferases
  • Granzymes