CD69-induced monocyte apoptosis involves multiple nonredundant signaling pathways

Cellular Immunology
R RamírezG Kroemer

Abstract

Simultaneous stimulation of human monocytes/macrophages or THP1 cells with LPS and an antibody specific for the activation marker CD69 induces apoptosis. Here we demonstrate the involvement of multiple independent signals that are necessary for apoptosis induction. Thus, inhibitors of phospholipase A2 and lipoxygenase prevent apoptosis induction. Similarly, the ADP-ribosylating G-protein-reactive pertussis toxin (PTX) but not a mutant toxin lacking the ADP-ribosylating moiety (mPTX) prevents apoptosis induction. Furthermore, inhibition of NO generation abrogates completely the induction of apoptosis by LPS/CD69 ligation. These three pathways can be dissociated from each other in the sense that interventions on the arachidonic acid metabolism or G proteins do not inhibit the generation of NO and that exogenous NO cannot reverse the inhibition of cell death by inhibitors of phospholipase A2 or PTX. In addition, both PTX and mPTX affect arachidonic acid mobilization only partially, indicating that the apoptosis-inhibitory effect of PTX (which is not shared by mPTX) cannot be explained by its effect on phospholipase A2 activation. Both LPS and anti-CD69 are sufficient on their own to activate cells, as determined by TNF production,...Continue Reading

Citations

May 23, 2013·PloS One·Thea K WöbkeBernd L Sorg
Mar 5, 2005·Trends in Immunology·David SanchoFrancisco Sánchez-Madrid
Aug 31, 1999·Immunopharmacology and Immunotoxicology·R MarzioS Betz-Corradin
Dec 26, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yanmei HanXuetao Cao
Jul 19, 2000·Archives of Biochemistry and Biophysics·J A Osés-PrietoM J López-Zabalza

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