Human milk oligosaccharides affect P-selectin binding capacities: In vitro investigation

Objective In the initial phase of cellular immune response, selectins mediate the emigration of leukocytes from the blood stream into inflammatory regions. Human milk oligosaccharides (HMOs) possess binding epitopes of selectin ligands such as sialyl Lewisx and sialyl Lewisa and therefore might impair the interaction of selectins with cellular ligands. Neutral, acidic, sialylated, or fucosylated HMO fractions with polymerization degrees of 3 to 50 were investigated regarding this interaction in a dynamic flow chamber model that considers physiologic shear stress conditions. Methods Human milk oligosaccharides were compared with κ-carrageenans and pectin oligosaccharides to deduce structure-activity relations. Fucoidan and sialyl Lewisx served as positive controls. Results All HMO fractions affected P-selectin ligand binding capacity but were not comparable to fucoidan. The activity of the acidic HMO fraction resembled sialyl Lewisx in decreasing the binding of the ligand to P-selectin. Conclusion Human milk oligosaccharides modulate rather than block the function of P-selectin.