Anti-Fas antibody induces different types of cell death in the human histiocytic cell line, U937, and the human B cell line, B104: the role of single-strand DNA breaks and poly (ADP-ribosyl)ation in cell death.
We investigated the anti-Fas antibody-induced cell death in two different types of human cell lines, U937 and B104. IFN-gamma increased the surface expression of Fas antigen and susceptibility to anti-Fas Ab-induced cell death of B104 and U937 cells. Anti-Fas Ab-induced death of U937 and B104 cells required neither a Ca2+ influx nor macromolecular synthesis. U937 cells treated with anti-Fas Ab represented apoptosis with DNA fragmentation, whereas anti-Fas Ab-treated B104 cells did not. Single-strand DNA breaks, however, appeared in the B104 cells. Zinc ions prevented DNA fragmentation and the morphological features of apoptosis in anti-Fas Ab-treated U937 cells, but did not inhibit cell death. However, zinc ions, when used in combination with the poly(ADP-ribosyl)ation inhibitors, inhibited anti-Fas Ab-induced U937 cell death. The inhibitors by themselves did not inhibit anti-Fas Ab-induced U937 cell death, but did inhibit anti-Fas Ab-induced B104 cell death. A substantial decrease in NAD pools was observed in anti-Fas Ab-treated B104 and U937 cells in parallel with the increase of DNA strand breaks before cell death became apparent. These results suggest the involvement of single-strand DNA breaks and poly(ADP-ribosyl)ation in the mechanisms of anti-Fas Ab-induced U937 and B104 cell death.
Sumimoto
S
S
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Ishigami
T
T
Horiguchi
Y
Y
Yonehara
S
S
Kanazashi
S
S
Heike
T
T
Katamura
K
K
Mayumi
M
M
D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D006644:Histiocytes / Q000166:cytology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009243:NAD / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology; D019014:fas Receptor
D000954:Antigens, Surface; D019014:fas Receptor; D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; D007371:Interferon-gamma; D015032:Zinc; D002118:Calcium