Research Abstract

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

Daniel E. Cramer 1,2, Stephanie Wagner 1,2,3, Bing Li 1, Jingjing Liu 1, Richard Hansen 1, Ryan Reca 4,Wan Wu 4, Ewa Zuba Surma 4, Damian Laber 3, Mariusz Z. Ratajczak 4, Jun Yan 1,3

Authors' Affiliations:  1 Tumor Immunobiology Program and 4 Stem Cell Institute, James Graham Brown Cancer Center, Department of Medicine, University of Louisville; 3 Division of Hematology/Oncology, Department of Medicine, James Graham Brown Cancer Center, University of Louisville

Stem Cells published online Mar 13, 2008; DOI: 10.1634/stemcells.2007-0712.

Abstract
Poly-(1,6)-β-D-glucopyranosyl-(1,3)-β-D-glucopyranose (PGG) β-glucan is a soluble yeast-derived polysaccharide that has been shown previously 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 to 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 to G-CSF treatment alone. Further studies demonstrated that neither complement 3 (C3) nor C receptor 3 (CR3) played a role in this effect and that PGG β-glucan treatment did not induce proinflammatory cytokine secretion. However,
bone marrow (BM) 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 non-hematopoietic cells contributed to MMP-9 secretion upon PGG β-glucan treatment.  Additonally, HPCs mobilized by PGG β-glucan had similar levels of engraftment in host and lineage differentiation capability compared to 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