Lysis of human monocytic leukemia cells by extracellular adenosine
triphosphate: mechanism and characterization of the adenosine triphosphate
receptor
E Spranzi, JY Djeu, SL Hoffman, PK Epling-Burnette and DK Blanchard
Department of Medical Microbiology & Immunology, University of South
Florida College of Medicine, H. Lee Moffitt Cancer Center and Research
Institute, Tampa 33612.
The present study shows that extracellular adenosine triphosphate (ATP) has
the capacity to mediate dose-dependent lysis of the monocytic leukemia cell
line THP-1. The lysis, assessed by 51Cr release, was found to be selective
for ATP, because adenosine diphosphate (ADP) or other nucleotides were less
effective in their ability to lyse the cells. The amount of 51Cr released
was particularly enhanced by the stimulation of the cells with 1,000 U/mL
of interferon gamma (IFN- gamma) for 3 days, and the sensitivity was time
and dose dependent. Analysis of the mechanism of lysis indicated that the
fully ionized form, ATP4-, mediated the lysis, because the addition of
cation chelators or the absence of the divalent cations, Ca2+ and Mg2+, in
the culture medium of a 6-hour 51Cr release assay increased the percent
specific lysis. Therefore, the ATP receptors on THP-1 cells were classified
as P2Z purinoceptors. Moreover, it is shown here that the Ca2+/calmodulin
complex plays a role in the regulation of the lysis by extracellular ATP of
THP-1 cells, because antagonists of this complex, such as trifluoperazine
or KN-62, were found to inhibit the ATP- mediated cell lysis.
Volume 82,
Issue 5,
pp. 1578-1585,
09/01/1993
Copyright © 1993 by The American Society of Hematology
