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 Lewis(x) and sialyl Lewis(a) 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 kappa-carrageenans and pectin oligosaccharides to deduce structure-activity relations. Fucoidan and sialyl Lewis(x) 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 Lewis(x) in decreasing the binding of the ligand to P-selectin.


CONCLUSIONS
Human milk oligosaccharides modulate rather than block the function of P-selectin.
Schumacher
Gabriele
G
Pharmacy, Pharmaceutical Chemistry, Rheinische Friedrich Wilhelms University Bonn, Bonn, Germany.
Bendas
Gerd
G
Stahl
Bernd
B
Beermann
Christopher
C
D001665:Binding Sites; D018395:CA-19-9 Antigen; D005732:Gangliosides; D006801:Humans; D066298:In Vitro Techniques; D007983:Lewis Blood Group Antigens; D008024:Ligands; D008895:Milk, Human / Q000737:chemistry* / Q000276:immunology; D009844:Oligosaccharides / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D000080506:Sialyl Lewis X Antigen; D013329:Structure-Activity Relationship
D018395:CA-19-9 Antigen; D005732:Gangliosides; D007983:Lewis Blood Group Antigens; D008024:Ligands; D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen; C064564:sialyl Le(a) ganglioside