Extracellular ATP inhibits apoptosis and maintains cell viability by inducing autocrine production of interleukin-4 in a myeloid progenitor cell line.
Interleukin-3 (IL-3)-dependent myeloid progenitor cell FDC.P2 is induced to undergo apoptotic cell death upon IL-3 depletion. Extracellular adenosine triphosphate (ATP) was found to prevent apoptosis and maintain cell viability of FDC.P2 cells upon IL-3 withdrawal. The antiapoptotic effect of ATP required extracellular Ca2+. Furthermore, FK506, a specific inhibitor of calcium/calmodulin-dependent protein phosphatase calcineurin, inhibited the antiapoptotic effect of ATP. As one of cytokines whose expression is dependent on the activation of calcineurin, interleukin-4 (IL-4) played a critical role in ATP-mediated cell survival of FDC.P2 cells because neutralizing antibody against IL-4 effectively abrogated the antiapoptotic activity of ATP. Moreover, ATP treatment induced a significant amount of secreted IL-4 that was sufficient to maintain cell viability. Taken together, our present results demonstrate that extracellular ATP triggers autocrine production of IL-4 through calcium-dependent activation of calcineurin and secreted IL-4 substitutes IL-3 in protecting FDC.P2 cells from apoptosis even in the absence of IL-3.
Palaga
Tanapat
T
Department of Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori, Yokohama 226, Japan. tanapat.p@chula.ac.th
Kataoka
Takao
T
Nagai
Kazuo
K
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D017077:Culture Media, Conditioned; D053938:DNA Fragmentation / Q000187:drug effects; D007377:Interleukin-3 / Q000172:deficiency; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D023461:Myeloid Progenitor Cells / Q000187:drug effects* / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D017077:Culture Media, Conditioned; D007377:Interleukin-3; D015847:Interleukin-4; D000255:Adenosine Triphosphate; D002118:Calcium; D016559:Tacrolimus