Mobilization of hematopoietic progenitor cells by yeast-derived beta-glucan requires activation of matrix metalloproteinase-9

Stem Cells. 2008 May;26(5):1231-40. doi: 10.1634/stemcells.2007-0712. Epub 2008 Mar 13.

Abstract

Poly-(1,6)-beta-d-glucopyranosyl-(1,3)-beta-d-glucopyranose (PGG) beta-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 beta-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 beta-glucan doses of 4.8-9.6 mg/kg. Animals treated with G-CSF and PGG beta-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 beta-glucan treatment did not induce proinflammatory cytokine secretion. However, bone marrow cells from PGG beta-glucan-treated mice secreted abundant matrix metalloproteinase-9 (MMP-9), and PGG beta-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 beta-glucan treatment. In addition, HPCs mobilized by PGG beta-glucan had similar levels of engraftment in host and lineage differentiation capability compared with those mobilized by G-CSF. Thus, PGG beta-glucan is an agent that enhances HPC mobilization and may improve the outcome of clinical stem cell transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / enzymology
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / drug effects
  • Chemokine CXCL12 / blood
  • Complement Activation / immunology
  • Complement C3 / immunology
  • Cytokines / metabolism
  • Enzyme Activation / drug effects
  • Female
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Mobilization*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / enzymology
  • Humans
  • Inflammation Mediators
  • Macrophage-1 Antigen / immunology
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Proteins
  • Saccharomyces cerevisiae / chemistry*
  • beta-Glucans / pharmacology*

Substances

  • Chemokine CXCL12
  • Complement C3
  • Cytokines
  • Inflammation Mediators
  • Macrophage-1 Antigen
  • Recombinant Proteins
  • beta-Glucans
  • poly-1-6-glucopyranosyl-1-3-glucopyranose glucan
  • Granulocyte Colony-Stimulating Factor
  • Matrix Metalloproteinase 9