B. Macino et al., CD45 REGULATES APOPTOSIS INDUCED BY EXTRACELLULAR ADENOSINE-TRIPHOSPHATE AND CYTOTOXIC T-LYMPHOCYTES, Biochemical and biophysical research communications, 226(3), 1996, pp. 769-776
Several lines of evidence implicate protein tyrosine phosphatases (PTP
) in the regulation of apoptotic cell death. We have evaluated the rol
e of CD45, the major PTP of hematopoietic cells, in apoptosis induced
by extracellular ATP (ATP(e)) and cytotoxic T lymphocytes (CTL). We ob
served that two CD45(-) clones obtained by mutagenesis of the Fas(-) c
ell line L1210, exhibit a higher susceptibility to apoptosis induced b
y ATP(e), which was also evident in Ca2+-free conditions, when compare
d to the parental cell line or CD45(+) variants. The CD45(-) cells wer
e also more susceptible to death mediated by an alloreactive CTL clone
. When the cytotoxic assay was performed in the presence of EGTA, a Ca
2+ chelator, which prevents cytotoxic granule exocytosis and perforin
polymerization on target cell membranes, only the CD45(-) target cells
were killed by the CTL clone. These results suggest that a cytotoxic
pathway other than the secretory or Fas-dependent pathways was respons
ible for the enhanced susceptibility of CD45(-) cells to death, and th
erefore provide further evidence for the role of ATP, as a possible me
diator of Ca2+-independent cell destruction by CTL. (C) 1996 Academic
Press, Inc.