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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-9-7
pubmed:abstractText
Adherence of hematopoietic progenitor cells (HPCs) to stroma is an important regulatory step in megakaryocytic differentiation. However, the mechanisms through which megakaryocytic progenitors are inhibited by stroma are poorly understood. We examined the role of sulfated glycoconjugates, such as proteoglycans (PGs), on human bone marrow stroma (hBMS). To this end, PG structure was altered by desulfation or enzymatic cleavage. PGs participated in adhesion of human HPC, as desulfation resulted in about 50% decline in adhesion to hBMS. Heparan sulfate proteoglycans (HSPGs) were found to be responsible by showing about 25% decline in adhesion after pre-incubation of HPC with heparin and about 15% decline in adhesion after enzymatic removal of HSPGs from hBMS. Furthermore, PGs were involved in binding cytokines. Both desulfation and enzymatic removal of stromal HSPGs increased release of megakaryocytopoiesis-inhibiting cytokines, that is, interleukin-8 (IL-8, 1.9-fold increase) and macrophage inflammatory protein-1alpha (MIP-1alpha, 1.4-fold increase). The megakaryocytic output of HPC grown in conditioned medium of desulfated stroma was decreased to 50% of the megakaryocytic output in CM of sulfated stroma. From these studies, it can be concluded that PGs in bone marrow, in particular HSPGs, are involved in binding HPC and megakaryocytopoiesis-inhibiting cytokines. Bone marrow stromal PGs thus reduce differentiation of HPC toward megakaryocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-4827
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Elsevier Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
383-92
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15350537-Acute Disease, pubmed-meshheading:15350537-Antigens, CD34, pubmed-meshheading:15350537-Blood Proteins, pubmed-meshheading:15350537-Bone Marrow, pubmed-meshheading:15350537-Cell Adhesion, pubmed-meshheading:15350537-Cell Differentiation, pubmed-meshheading:15350537-Cells, Cultured, pubmed-meshheading:15350537-Chemokine CCL3, pubmed-meshheading:15350537-Chemokine CCL4, pubmed-meshheading:15350537-Culture Media, Conditioned, pubmed-meshheading:15350537-Eosinophil Major Basic Protein, pubmed-meshheading:15350537-Hematopoietic Stem Cells, pubmed-meshheading:15350537-Heparitin Sulfate, pubmed-meshheading:15350537-Humans, pubmed-meshheading:15350537-Interleukin-8, pubmed-meshheading:15350537-Leukemia, Myeloid, pubmed-meshheading:15350537-Lymphoma, Non-Hodgkin, pubmed-meshheading:15350537-Macrophage Inflammatory Proteins, pubmed-meshheading:15350537-Megakaryocytes, pubmed-meshheading:15350537-Proteoglycans, pubmed-meshheading:15350537-Stromal Cells
pubmed:year
2004
pubmed:articleTitle
Bone marrow stromal proteoglycans regulate megakaryocytic differentiation of human progenitor cells.
pubmed:affiliation
Department of Hematology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands. s.zweegman@vumc.nl
pubmed:publicationType
Journal Article