Rapid hematopoietic progenitor mobilization by sulfated colominic acid.
Hematopoietic progenitor cells (HPCs) can be mobilized from bone marrow (BM) to the blood by G-CSF. In this process, CXCR4 and CD26 play critical roles. Sulfated colominic acid (SCA) inhibits HIV entry, the step which requires CXCR4 and CD26 as co-receptors. Thus, we hypothesized that SCA would modulate HPC trafficking. We first found that SCA mobilized HPCs rapidly via CD26-independent mechanism. In vitro progenitor migration toward chemokine SDF-1 was significantly enhanced by SCA, and it was completely abrogated by CXCR4 inhibition. This likely originated from the inhibition of CXCR4 down-regulation after interaction with SDF-1. Serum SDF-1 level increased after SCA injection, whereas no change was observed in BM and bone. These results suggest that SCA induces HPC mobilization by modulating CXCR4 function resulting in attraction toward increased SDF-1 in the circulation. Furthermore, we confirmed an additive effect with G-CSF in mobilization. SCA may provide an efficacy in clinical mobilization.
Kubonishi
Shiro
S
Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kikuchi
Tomoko
T
Yamaguchi
Shinya
S
Tamamura
Hirokazu
H
Fujii
Nobutaka
N
Watanabe
Takeshi
T
Arenzana-Seisdedos
Fernando
F
Ikeda
Kazuma
K
Matsui
Toshimitsu
T
Tanimoto
Mitsune
M
Katayama
Yoshio
Y
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011134:Polysaccharides / Q000494:pharmacology*; D019718:Receptors, CXCR4 / Q000378:metabolism; D013997:Time Factors
C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D011134:Polysaccharides; D019718:Receptors, CXCR4; C463021:sulfated colominic acid