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Binding of primitive hematopoietic progenitor cells to marrow stromal cells
involves heparan sulfate
M Siczkowski, D Clarke and MY Gordon
Leukaemia Research Fund Centre, Institute of Cancer Research, London, UK.
Blast colony-forming cells (BI-CFC) and pre-colony-forming unit-
granulocyte, monocyte (CFU-GM) in human bone marrow bind to marrow- derived
stromal layers grown in the presence of methylprednisolone (MP+), but do
not bind to stroma grown without MP (MP-). The BI-CFC bind to stroma and
form colonies when overlaid with agar; the pre-CFU- GM bind to stroma and
release CFU-GM into the supernatant culture medium (delta assay). These two
classes of progenitor may represent similar stages of hematopoietic cell
development. Their binding to stroma depends on the presence of heparan
sulfate proteoglycan (HS-PG) in the extracellular matrix secreted by the
stromal cells. Here, we have analyzed the functional and biochemical
properties of HS-PG isolated from MP+ and MP- stromal cultures. HS-PG or
isolated HS glycosaminoglycan (GAG) side chains partially blocked
progenitor cell binding when they were added to the 2-hour binding phase of
the BI-CFC or delta assays. Gel electrophoresis of HS-PG resolved more
bands in matrix preparations from MP+ cultures than in preparations from
MP- cultures. The blocking activity of the eluted MP+ HS-PG bands depended
partly on the amount of GAG attached to the protein core and presumably
partly on the structure of the core itself. Time course studies
demonstrated that the HS-dependent phase of the binding interaction was
limited to the first 30 to 60 minutes of the 2-hour binding phase. The
different blocking effects of MP+ and MP- HS indicate that they have
different biochemical properties. The HS-GAG in MP+ stroma has a higher
degree of sulfation and a greater negative charge to mass ratio compared
with MP- HS-GAG. Variations in HS may determine specific binding by
hematopoietic progenitor cells and a heparan sulfate receptor is envisaged
as acting in concert with further cell adhesion molecules (CAMs) on the
progenitor cell surface.
Volume 80,
Issue 4,
pp. 912-919,
08/15/1992
Copyright © 1992 by The American Society of Hematology
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