Rapid hematopoietic progenitor mobilization by sulfated colominic acid |
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Authors: | Kubonishi Shiro Kikuchi Tomoko Yamaguchi Shinya Tamamura Hirokazu Fujii Nobutaka Watanabe Takeshi Arenzana-Seisdedos Fernando Ikeda Kazuma Matsui Toshimitsu Tanimoto Mitsune Katayama Yoshio |
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Affiliation: | Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. |
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Abstract: | 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. |
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Keywords: | Hematopoietic stem/progenitor cells SDF-1/CXCL12 CXCR4 Mobilization Sulfated colominic acid G-CSF |
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