Enhanced mobilization of hematopoietic progenitor cells by mouse MIP-2 and granulocyte colony-stimulating factor in mice.
Human interleukin-8 (IL-8) induces a rapid mobilization of hematopoietic progenitor cells (HPCs) into peripheral blood in mice and primates. Because an exact homologue of human IL-8 does not exist in mice, a chemokine, macrophage inflammatory protein-2 (MIP-2), is supposed to substitute the function of IL-8 in mice. Hence, we investigated the capacity of mouse MIP-2 to induce HPC mobilization in mice. Mouse MIP-2 induced, in either untreated or splenectomized mice, a rapid HPC mobilization, as evidenced by increased numbers of colony-forming unit granulocyte-macrophage (CFU-GM) and lineage marker (Lin)-c-kit+Sca-1+ cells. Although release of elastase from activated neutrophils was proposed to be involved in IL-8-induced HPC mobilization, mouse MIP-2 induced similar levels of HPC mobilization in elastase-deficient beige mice at a similar level to normal ones. This HPC mobilization by MIP-2 was markedly enhanced by pretreatment with granulocyte-colony-stimulating factor (G-CSF). Moreover, the combination of G-CSF and MIP-2 apparently down-regulated L-selectin expression on Lin-Sca-1+ cells in peripheral blood as well as bone marrow. Thus, MIP-2 may down-modulate the interaction between HPCs and bone marrow stroma by reducing L-selectin expression on HPCs and cause rapid mobilization of HPCs into peripheral blood.
Wang
J
J
Department of Pharmacology, Cancer Research Institute, Japan.
Mukaida
N
N
Zhang
Y
Y
Ito
T
T
Nakao
S
S
Matsushima
K
K
D000818:Animals; D015415:Biomarkers; D054426:Chemokine CXCL2; D002630:Chemotactic Factors / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000494:pharmacology*; D015536:Down-Regulation; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019041:L-Selectin / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015846:Monokines / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
D015415:Biomarkers; D054426:Chemokine CXCL2; D002630:Chemotactic Factors; D016207:Cytokines; D015846:Monokines; D011994:Recombinant Proteins; D019041:L-Selectin; D016179:Granulocyte Colony-Stimulating Factor