T. Netelenbos et al., Differences in sulfation patterns of heparan sulfate derived from human bone marrow and umbilical vein endothelial cells, EXP HEMATOL, 29(7), 2001, pp. 884-893
Objective. Heparan sulfates (HS), the polysaccharide side chains of HS prot
eoglycans, differ in structure and composition of sulfated domains among va
rious tissue types, resulting in selective protein binding. HS proteoglycan
s on bone marrow endothelial cells (BMEC) could contribute to tissue specif
icity of the bone marrow endothelium and play a role in the presentation of
chemokines such as stromal cell-derived factor-1 (SDF-1) and adhesion of h
ematopoietic progenitor cells after stem cell transplantations. We characte
rized differences in HS structure and SDF-1 binding between BMEC and human
umbilical vein endothelial cells (HUVEC).
Materials and Methods. Expression of HS proteoglycans on human hone marrow
microvessels was investigated by immunohistochemical staining. Comparison o
f three human BMEC cell lines with HUVEC and an HUVEC cell line was studied
by now cytometry using antibodies against different epitopes of the HS pol
ysaccharide chain. HS proteoglycans were biochemically characterized after
isolation from metabolically labeled cultures of the BMEC cell line 4LHBMEC
and HUVEC. Binding of radiolabeled SDF-1 to 4LHBMEC and HUVEC and competit
ion with heparins were investigated,
Results. Bone marrow microvessels constitutively expressed HS proteoglycans
. Flow cytometric experiments showed differences in HS chain composition be
tween BMEC and HUVEC. Biochemical characterization revealed more O-sulfatio
n of the N-sulfated domains present in cell-associated HS glycosaminoglycan
s in 4LHBMEC compared to HUVEC. Binding experiments showed that 4LHBMEC bou
nd more (125)[I]SDF-1 per cell than HUVEC. This could be inhibited largely
by heparin and O-sulfated heparin and to a lesser extent hy N-sulfated hepa
rin,
Conclusions. Cellular HS from BMEC differs in composition from HUVEC. We po
stulate that the presence of highly sulfated domains in the HS chains from
BMEC contributes to tissue specificity of bone marrow endothelium in which
HS may be involved in SDF-1 presentation and adhesion of hematopoietic prog
enitor cells. (C) 2001 International Society for Experimental Hematology. P
ublished by Elsevier Science Inc.