[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.
Peng
L
L
Department of Laboratory Medicine, School of Medicine, West China University of Medical Sciences, Chengdu.
Bradley
C J
CJ
Wiley
J S
JS
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