[Apoptosis of leukemic lymphocytes mediated by purinergic P2z receptors].
OBJECTIVE
To investigate the role of purinergic P2z receptors for apoptosis of human leukemic lymphocytes induced by extracellular adenosine triphosphate (ATP).


METHODS
A total of 11 B-CLL patients were studied with regard to exposure of leukemic lymphocytes with (n = 8) or without (n = 3) P2z receptors to ATP, benzoylbenzoic-ATP (BzATP), 2-methylthio-ATP (2MeSATP), adenosine-5'-[gamma-thio] triphosphate (ATP-gamma S), and other nucleosides for 8 h in vitro. Apoptosis was detected by electron microscopy (EM), agarose gel electrophoresis, and quantitative assay-TdT assay.


RESULTS
Apoptosis was detected only in leukemic lymphocytes with P2z receptors. Using a quantitative assay, we found that ATP-induced DNA strand breaks occur specifically with BzATP, ATP and 2MeSATP, but not for analogue ATP-gamma S nor other nucleosides. Meanwhile, ATP-induced DNA fragmentation was fully blocked by pretreatment with oxidized ATP (OxATP), a compound recently shown to block P2z receptors. Also, the Ca2+/calmodulin complex played a role in the regulation of the apoptosis induced by ATP on CLL cells, because an antagonist of this complex, 1-[N,O-bis (5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) was found to inhibit the ATP-induced apoptosis.


CONCLUSIONS
These data indicate that P2z receptors on lymphocytes play an important role in apoptosis induced by ATP in vitro.
Department of Laboratory Medicine, School of Medicine, West China University of Medical Sciences, Chengdu.
L
L
Peng
C J
CJ
Bradley
J S
JS
Wiley
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D014407:Tumor Cells, Cultured
D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate