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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-08-2588.

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2002-08-2588v1
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Submitted August 27, 2002
Accepted October 17, 2002

Identification of a macrophage inflammatory protein-1{alpha} (MIP-1{alpha}) binding heparan sulfate oligosaccharide that supports long-term in vitro maintenance of human LTC-IC

Sally E Stringer, Matthew S Nelson, and Pankaj Gupta*

Paterson Institute for Cancer Research, Manchester, United Kingdom
Hematology/Oncology Section, VA Medical Center, Minneapolis, MN, USA
Division of Hematology-Oncology-Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Genetics, Cell Biology & Development, University of Minnesota Medical School, Minneapolis, MN, USA

* Corresponding author; email: gupta013{at}tc.umn.edu.

We previously showed that heparan sulfate (HS) is required for in vitro, cytokine + chemokine mediated maintenance of primitive human hematopoietic progenitors. However, HS preparations are mixtures of polysaccharide chains of varying size, structure and protein-binding abilities. We therefore examined if the LTC-IC supportive capability of HS is attributable to an oligosaccharide of defined length and protein binding ability. Oligosaccharides of a wide range of sizes were prepared, and their capability to support human marrow LTC-IC maintenance in presence of low dose cytokines and a single chemokine (MIP-1{alpha}) was examined. LTC-IC supportive capability of HS oligosaccharides correlated directly with size and MIP-1{alpha} binding ability. A specific, MIP-1{alpha} binding HS oligosaccharide preparation of Mr 10 kD that optimally supported LTC-IC maintenance was identified. This oligosaccharide possessed the structure required for MIP-1{alpha} binding, which we have recently described. The present study defines the minimum size and structural features of LTC-IC supportive HS.


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