Stem Cells
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

First published online March 13, 2008
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2007-0712v1
2007-0712v2    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Google Scholar
Right arrow Articles by Cramer, D. E.
Right arrow Articles by Yan, J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cramer, D. E.
Right arrow Articles by Yan, J.
Submitted on August 27, 2007
Accepted on March 5, 2008

THE STEM CELL NICHE

Mobilization of Hematopoietic Progenitor Cells by Yeast-derived {beta}-Glucan Requires Activation of Matrix Metalloproteinase-9

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

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

* To whom correspondence should be addressed. E-mail: jun.yan{at}louisville.edu.


  Abstract

Poly-(1,6)-{beta}-D-glucopyranosyl-(1,3)-{beta}-D-glucopyranose (PGG) {beta}-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 {beta}-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 {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 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 {beta}-glucan treatment did not induce proinflammatory cytokine secretion. However, bone marrow (BM) 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 non-hematopoietic cells contributed to MMP-9 secretion upon PGG {beta}-glucan treatment. Additionally, HPCs mobilized by PGG {beta}-glucan had similar levels of engraftment in host and lineage differentiation capability compared to 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.

______________________________________________________________________________

D. Cramer and S. Wagner contributed equally to this work.

 Key Words. Hematopoietic progenitor cells, mobilization, {beta}-glucan, matrix metalloproteinase-9






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
STEM CELLS THE ONCOLOGIST CME ALPHAMED PRESS JOURNALS
Email Content Delivery
Copyright © 2008 by AlphaMed Press.