Inhibitory effects of carrier-immobilized synthetic histo-blood group A-, B-, H-, and SiaLe-oligosaccharides on H2O2 generation by human polymorphonuclear leukocytes

Carbohydrate-bearing polymers of biologically inert design are versatile tools to delineate functional aspects of oligosaccharides. Binding of synthetic N-substituted polyacrylamide (PAA) conjugates of histo-blood group (A_di, A_tri, B_di, B_tri, H_di, SiaLe^a, and SiaLe^x) to human polymorphonuclear leukocytes (PMNs), and effects on H₂O₂ generation elicited by different agonists such as digitonin, N-formyl-Met-Leu-Phe (FMLP) and the galactoside-specific lectin from Viscum album L. (VAA) were assessed. PMNs expressed binding sites for blood group-related neoglycoconjugates in the range of N10⁶–10⁷/cell with K_D-values in the μM range. Treatment of PMNs (2×10⁶ cells/ml) with PAA-probes (50 μg/ml) for 5 min did not activate the “respiratory burst”. However, it led to suppression (range 20–70%) of H₂O₂ generation of cells in the presence of elicitors. In detail, the FMLP-induced response was significantly decreased by A_di, A_tri, B_tri, H_di, SiaLe^a, and SiaLe^x conjugates, whereas for digitonin one only by A_di, A_tri, B_tri. All the seven tested PAA-probes were found to inhibit significantly VAA-mediated release of H₂O₂ from PMNs. In this case, interference can take place already, at the stage of initial binding, especially for B- and H-epitopes, but less prominently for A- and SiaLe-epitopes. These results support the notion that PAA-immobilized histo-blood group oligosaccharides can serve as effector molecules with the ability to reduce the H₂O₂-generation of PMNs, warranting further studies on the involved reaction pathway.