Mobilization of Hematopoietic Progenitor Cells by Yeast-Derived β-Glucan Requires Activation of Matrix Metalloproteinase-9

Abstract

Abstract Poly-(1,6)-β-d-glucopyranosyl-(1,3)-β-d-glucopyranose (PGG) β-glucan is a soluble yeast-derived polysaccharide that has previously been shown to induce hematopoietic progenitor cell (HPC) mobilization. However, the mobilizing mechanism of action remains unknown. Here, we confirmed that PGG β-glucan alone or in combination with granulocyte colony-stimulating factor (G-CSF) mobilizes HPC into the periphery. Optimal mobilizing effects were seen 24–48 hours after PGG β-glucan doses of 4.8–9.6 mg/kg. Animals treated with G-CSF and PGG β-glucan showed a collaborative effect in HPC mobilization compared with G-CSF treatment alone. Additional studies demonstrated that neither complement 3 nor complement receptor 3 played a role in this effect and that PGG β-glucan treatment did not induce proinflammatory cytokine secretion. However, bone marrow cells from PGG β-glucan-treated mice secreted abundant matrix metalloproteinase-9 (MMP-9), and PGG β-glucan-induced HPC mobilization was abrogated in MMP-9 knockout mice. Moreover, we demonstrated that both hematopoietic and nonhematopoietic cells contributed to MMP-9 secretion upon PGG β-glucan treatment. In addition, HPCs mobilized by PGG β-glucan had similar levels of engraftment in host and lineage differentiation capability compared with those mobilized by G-CSF. Thus, PGG β-glucan is an agent that enhances HPC mobilization and may improve the outcome of clinical stem cell transplantation. Disclosure of potential conflicts of interest is found at the end of this article.