E. Bruno et al., MARROW-DERIVED HEPARAN-SULFATE PROTEOGLYCAN MEDIATES THE ADHESION OF HEMATOPOIETIC PROGENITOR CELLS TO CYTOKINES, Experimental hematology, 23(11), 1995, pp. 1212-1217
Heparan sulfate proteoglycan (HS-PG), an important component of the hu
man bane marrow extracellular matrix (ECM), is believed to influence h
ematopoietic progenitor cell development by binding and localizing gro
wth factors to specific niches within the hematopoietic microenvironme
nt. We utilized a model ECM system, which uses immobilized ECM protein
s and/or cytokines and bone marrow populations enriched for human hema
topoietic stem cells (HSC), to assess the effects of HS-PG on the deve
lopment of primitive hematopoietic progenitor cells. HS-PG alone faile
d to bind hematopoietic progenitor cells cloned from bone marrow CD34(
+)CD15(-)HLA-DR(-) cells, which are enriched for HSC. HS-PG alone fail
ed to function as a mitogen. In sharp contrast, the interaction of HS-
PG with either growth factors (interleukin-3 [IL-3] or stem cell facto
r/Kit ligand [KL]) or an ECM protein (thrombospondin [TSP]) markedly i
nfluenced progenitor cell adherence. The binding of either IL-3 or KL
to HS-PG resulted in a two-fold increase in attachment of the colony-f
orming unit-granulocyte/macrophage (CFU-GM), a 1.5-fold increase in at
tachment of the burst-forming unit-erythroid (BFU-E) and the high-prol
iferative-potential colony-forming cell (HPP-CFC), and a two- to three
-fold increase in attachment of the colony-forming nit-granulocyte/ery
throid/macrophage/megakaryocyte (CFU-GEMM) compared to localized growt
h factor alone. Attachment of the BFU-megakaryocyte (BFU-MK), however,
was slightly reduced by the interaction of either IL-3 or KL with HS-
PG. The interaction of HS-PG with TSP resulted in a two-fold increase
in CFU-GM and CFU-GEMM attachment, while the attachment of BFU-E, HPP-
CFC, and BFU-MK was unaltered. We conclude that HS-PG cooperatively in
teracts with both growth factors and ECM proteins to augment progenito
r cell localization within the hematopoietic microenvironment.