Extracellular ATP is involved in the induction of apoptosis in murine hematopoietic cells.
Extracellular nucleotides have multiple biological actions in processes such as proliferation, differentiation, chemotaxis, and cytokine secretion through P2X receptors on the cell surface. To determine the biological activity of adenosine triphosphate (ATP) and the expression of P2 nucleotide receptors in murine bone marrow-derived hematopoietic cells and stem cells/progenitor cells, we investigated the effects of ATP in assays of cell proliferation and cell death in vitro. Our results demonstrated that several subtypes of P2X receptors were expressed on hematopoietic cells and that P2X7, in particular, was partially expressed in hematopoietic stem cells/progenitor cells. In addition, stimulation of hematopoietic cells with high concentrations of ATP caused severe inhibition of cell proliferation despite the presence of cytokine stimulation. We analyzed the apoptotic effects of stimulation with several different dosages of ATP and confirmed the enhanced apoptotic activity in hematopoietic cells and progenitor cells. Antagonists, against P2X receptors and ATP, suramin and oxidized ATP, inhibited the induction of cell death for murine hematopoietic cells. Our data suggest that extracellular nucleotides may provide a novel and powerful tool for regulating the cell fate of hematopoietic stem cells.
Yoon
Mi-Jung
MJ
Cell and Gene Therapy Research Institute, Graduate School of Life Science and Biotechnology, Pochon CHA University, Korea.
Lee
Hyun-Joo
HJ
Lee
Yong-Soo
YS
Kim
Jae-Hwan
JH
Park
Jin-Ki
JK
Chang
Won-Kyong
WK
Shin
Ho-Chul
HC
Kim
Dong-Ku
DK
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000166:cytology; D006413:Hematopoietic System / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058469:Receptors, Purinergic P2X; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D013977:Tibia / Q000166:cytology
D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D013498:Suramin; D000255:Adenosine Triphosphate