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 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.
Nardini
Elena
E
Department of Experimental Oncology and Laboratories, Molecular Targeting Unit, Medicine Laboratory Unit and Unit of Medical Statistics and Biometry, National Cancer Institute, Milan, Italy.
Morelli
Daniele
D
Aiello
Piera
P
Besusso
Dario
D
Calcaterra
Claudia
C
Mariani
Luigi
L
Palazzo
Marco
M
Vecchi
Annunciata
A
Paltrinieri
Saverio
S
Menard
Sylvie
S
Balsari
Andrea
A
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D054426:Chemokine CXCL2; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood; D015603:Keratinocytes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*
C408982:CPG-oligonucleotide; D054426:Chemokine CXCL2; D016209:Interleukin-8; D015846:Monokines; D009838:Oligodeoxyribonucleotides; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor