Differences between ATP-mediated cytotoxicity and cell-mediated cytotoxicity.
There has been considerable recent interest in the possible role of extracellular ATP in cell-mediated cytotoxicity. To investigate the similarities and differences between ATP-mediated lysis and CTL-mediated lysis, we studied in detail the ATP-mediated lysis of EL-4 cells, which are highly susceptible to lysis by extracellular ATP. ATP-mediated lysis was time and concentration dependent; most lysis occurred within 4 to 6 h of incubation. The kinetics of ATP- and cell-mediated lysis were similar. However, in contrast to CTL-mediated lysis, ATP-mediated lysis of EL-4 cells did not appear to be accompanied by characteristic chromosomal degradation (apoptosis). In order to compare these cytotoxic processes in greater detail, ATP-resistant clones were derived by growing EL-4 cells continuously in the presence of high concentrations of ATP. These cloned EL-4 lines showed marked resistance to ATP-mediated cytotoxicity across a wide range of concentrations but were as susceptible as the parent EL-4 cells to cell-mediated cytotoxicity by an alloreactive effector population from a MLC. Thus, there appear to be a number of differences between ATP-mediated and cell-mediated cytotoxicity in this system; most notable is the identification of cell lines that are resistant to ATP but susceptible to CTL-mediated lysis.
Avery
R K
RK
Infectious Disease Unit Children's and Medical Services, Massachusetts General Hospital, Boston 02114.
Bleier
K J
KJ
Pasternack
M S
MS
D000255:Adenosine Triphosphate / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D003602:Cytotoxicity, Immunologic; D004249:DNA Damage; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000255:Adenosine Triphosphate