CpG-oligodeoxynucleotides induce mobilization of hematopoietic progenitor cells into peripheral blood in association with mouse KC (IL-8) production

The immune system of vertebrates detects bacterial DNA as a "danger signal" based on the presence of unmethylated CpC motifs. We examined whether oligodeoxynucleotides (ODNs) with CpC motifs (CpC-ODNs) also induce mobilization of hematopoietic progenitor cells (HPCs). Mice challenged with CpC-ODNs showed an increase in peripheral blood colony-form ing units (CFU) with a peak at day 4 after treatment, associated with an increase, starting 30 min after CpC treatment, in serum levels of mouse keratinocyte-derived chemokine (mKC), a functional homolog of human interleukin (IL) 8; production of granulocyte-colony-stimulating factor (CSF) was also detected. Mobilization and mKC induction were sequence-specific and dose-dependent occurring even with low doses of CpC-ODNs. Interestingly, intestinal cells were involved in mKC production. HPC mobilization by CpG-ODNs was dependent on peripheral blood mononuclear cells since mobilization was reduced in neutrophil-depleted mice. Moreover, CpC-ODN treatment significantly increased C-CSF mobilizing capacity. Finally, pretreatment with an anti-mKC neutralizing antibody significantly reduced CpC-induced mobilization, further supporting a role for mKC. Thus, bacterial DNA is a "danger signal" not only for immune cells but also for hematopoietic cells, communicating the need for increased hematopoiesis during infections and for the renewal of the immune system. The HPC mobilization activity of CpC-ODNs will need to be considered in the design of treatment regimens for cancer clinical trials using CpC-ODNs in association with chemotherapy. (copyright) 2005 Wiley-Liss, Inc.