Immunostimulatory CpG-oligodeoxynucleotides cause extramedullary murine hemopoiesis.
Bacterial DNA and the synthetic CpG-oligodeoxynucleotides (ODNs) derived thereof have attracted attention because they activate cells of the adaptive immune system (lymphocytes) and the innate immune system (APCs) in a sequence-dependent manner. Here, we addressed whether CpG-ODNs affect hemopoiesis. Challenging mice with immunostimulatory CpG-ODN sequences led to transient splenomegaly, with a maximum increase of spleen weight at day 6. The induction of splenomegaly by CpG-ODNs was sequence-specific, dose-dependent, and associated with an increase in splenic cell count, in numbers of granulocyte-macrophage CFUs (GM-CFUs), and early erythroid progenitors (burst-forming units-erythroid). The transfer of spleen cells from CpG-ODN-pretreated animals into lethally irradiated syngeneic mice yielded an increase of spleen CFUs. Furthermore, the challenge of sublethally irradiated mice with CpG-ODNs caused radioprotective effects, in that recovery of GM-CFUs and cytotoxic T cell function was enhanced. The increase in GM-CFU and CTL function correlated with an enhanced resistance to Listeria infection in irradiated mice. We conclude from these data that CpG-ODNs trigger extramedullary hemopoiesis, and that this finding could be of therapeutic relevance in myelosuppression.
Sparwasser
T
T
Institute of Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, Germany.
Hültner
L
L
Koch
E S
ES
Luz
A
A
Lipford
G B
GB
Wagner
H
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D018899:CpG Islands / Q000276:immunology*; D005260:Female; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016513:Mice, SCID; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology; D011828:Radiation Chimera / Q000276:immunology; D011837:Radiation-Protective Agents / Q000494:pharmacology; D013163:Splenomegaly / Q000276:immunology / Q000473:pathology