Synthetic CpG oligonucleotides as potential modulators of neutrophil survival in PAMP-associated inhibition of apoptosis.

We studied the effects of a synthetic CpG oligonucleotide (CpG ODN2006) on polymorphonuclear leukocyte (PMNL, neutrophil) survival and oxidant status. CpG ODN2006 showed a dose-dependent effect on the apoptosis of resting neutrophils. Without affecting the viability of resting cells, low concentrations of CpG ODN2006 interfered with Salmonella typhimurium-mediated viability prolongation and increased neutrophil apoptosis to control levels. CpG ODN2006 stimulated neutrophil apoptosis by enhancing ROS generation. Even small doses of ODN could induce the production of intracellular superoxide anions. The high superoxide reactogenicity, including with respect to nitrogen oxide, led to increased levels of intracellular ROS and RNS, which ultimately caused apoptosis. The pro-oxidant effect of low concentrations of CpG ODN2006 was not sufficient to trigger irreversible pro-apoptotic mechanisms. However, the sensitivity of PMNLs to ODN2006, a modulator of apoptosis, increased significantly under conditions of infectious inflammation. Inactivated S. typhimurium proved to be suitable for simulating inflammatory conditions in vitro.