Premium
CpG‐oligodeoxynucleotides induce mobilization of hematopoietic progenitor cells into peripheral blood in association with mouse KC (IL‐8) production
Author(s) -
Nardini Elena,
Morelli Daniele,
Aiello Piera,
Besusso Dario,
Calcaterra Claudia,
Mariani Luigi,
Palazzo Marco,
Vecchi Annunciata,
Paltrinieri Saverio,
Menard Sylvie,
Balsari Andrea
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20360
Subject(s) - cpg site , cpg oligodeoxynucleotide , haematopoiesis , immune system , peripheral blood mononuclear cell , progenitor cell , chemokine , biology , immunology , cancer research , bone marrow , hematopoietic growth factor , stem cell , microbiology and biotechnology , dna methylation , in vitro , gene , gene expression , biochemistry
Abstract The immune system of vertebrates detects bacterial DNA as a “danger signal” based on the presence of unmethylated CpG motifs. We examined whether oligodeoxynucleotides (ODNs) with CpG motifs (CpG‐ODNs) also induce mobilization of hematopoietic progenitor cells (HPCs). Mice challenged with CpG‐ODNs showed an increase in peripheral blood colony‐forming units (CFU) with a peak at day 4 after treatment, associated with an increase, starting 30 min after CpG 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 CpG‐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, CpG‐ODN treatment significantly increased G‐CSF mobilizing capacity. Finally, pretreatment with an anti‐mKC neutralizing antibody significantly reduced CpG‐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 CpG‐ODNs will need to be considered in the design of treatment regimens for cancer clinical trials using CpG‐ODNs in association with chemotherapy. © 2005 Wiley‐Liss, Inc.