Chemistry Reference
In-Depth Information
1996; Obermeier et al., 1999). It follows that they may alter protein-carbohy-
drate interactions also at a systemic level. For example, recent studies suggest
that human milk oligosaccharides interfere with the adhesion of neutrophils to
vascular endothelial cells (Klein et al., 2000) and platelets (Bode et al., 2004).
These effects appear to be based on the structural resemblance of some human
milk oligosaccharides to the glycoprotein ligands of selectins. Selectins are
trans-membrane proteins that are involved in cell-cell interactions in the
immune system. P-selectin mediates leukocyte deceleration (rolling) on acti-
vated endothelial cells and initiates leukocyte extravasation at sites of inflam-
mation. P-selectin is also involved in the formation of platelet-neutrophil
complexes (PNC), a sub-population of highly activated neutrophils primed
for adhesion, phagocytosis and enhanced production of reactive oxygen spe-
cies. Recent studies suggest that oligosaccharides containing sialyl Le
x
or its
stereoisomer sialyl Le
a
, which resemble the P-selectin ligand, inhibit the bind-
ing of selectin ligands to the surface of endothelial cells and platelets; this
interferes with the formation of PNC, the effect of which is anti-inflammatory.
The following oligosaccharide fractions were tested in vitro to establish whether
they reduce leukocyte deceleration on U937 cells, which express the P-selectin
ligand: total human milk oligosaccharides, neutral oligosaccharides, total
acidic oligosaccharides, neutral oligosaccharides with a polymerization degree
of 4, fucosylated oligosaccharides and disialyl lacto-N-tetraose. The acidic
oligosaccharides fraction produced a slight but definite reduction of P-selectin
ligand binding, similar to that of standard sialyl Le
x
, whereas the total neutral
oligosaccharides and neutral fucosylated oligosaccharides fractions did not
(Schumacher et al., 2006). These results support the notion of anti-inflamma-
tory effects of acidic human milk oligosaccharides.
However, Klein et al. (2000) showed that, in vitro, the neutral milk
oligosaccharide fraction can inhibit the binding of neutrophils to TNF-sti-
mulated endothelium and that the whole milk oligosaccharides fraction
enhanced the formation of platelet-neutrophil complexes (Klein et al., 2000).
It has been reported that the incidence of necrotizing enterocolitis, a
condition which is considered to be an exaggerated immune response, is
about 85% lower in breast-fed than in formula-fed infants. This is consistent
with an anti-inflammatory effect of absorbed human milk oligosaccharides
(Lucas and Cole, 1990).
Another potential human milk oligosaccharide target could be DC-
SIGN (dendritic cell-specific intercellular adhesion molecule-grabbing non-
integrin). This is expressed on dendritic cells (DC) in the intestine and other
tissues and is involved in the capture of different pathogens, including HIV-1,
hepatitis C, cytomegalovirus, Dengue virus, Mycobacterium and Candida
albicans. Unidentified components in human milk bind to DC-SIGN and
inhibit HIV-1 transfer to CD4+ T lymphocytes. DC-SIGN has high affinity
