Summary
Excessive leukocyte infiltration causes severe tissue damage in a variety of inflammatory
diseases. The initial step in leukocyte extravasation is mediated by selectins and
oligosaccharides on their glycoconjugate ligands. Human milk is a rich source of lactose-derived
oligosaccharides that are partly absorbed in the intestine and excreted with the urine.
As these components contain binding determinants for the selectins we investigated
whether human milk oligosaccharides are able to affect leukocyte rolling and adhesion
to endothelial cells under dynamic conditions. Therefore, monocytes, lymphocytes,
or neutrophils isolated from human peripheral blood were passed over TNF-α-activated
HUVEC under shear stress. The influence of different oligosaccharide fractions was
determined by video-micros-copy and compared with the effects of various individual
oligosaccharides. Within a physiological range (12.5-125 µg/ml) the acidic fraction
significantly inhibited leukocyte rolling and adhesion (up to 24.0% and 52.8%, respectively)
in a concentrationdependent manner. These effects were even more pronounced than those
achieved by soluble sialyl-Lewis x, a physiological binding determinant for selectins.
Several active components within the oligosaccharide fraction of human milk were identified,
e.g. 3’-sialyl-lactose and 3’-sialyl-3-fucosyl-lactose. These results indicate that
specific oligosaccharides in human milk may serve as anti-inflammatory components
and might therefore contribute to the lower incidence of inflammatory diseases in
human milk-fed infants.
Keywords
Selectins - leukocytes - oligosaccharides - human milk - inflammation