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 to ols to delineate functional aspects of oligosaccharides. Binding of synthet ic N-substituted polyacrylamide (PAA) conjugates of histo-blood group (A(di ), Am, B-di. B-tri, H-di, SiaLe(a), and SiaLe(x)) to human polymorphonuclea r leukocytes (PMNs), and effects on H2O2 generation elicited by different a gonists such as digitonin, N-formyl-Met-Leu-Phe (FMLP) and the galactoside- specific lectin from Viscum album L. (VAA) were assessed. PMNs expressed bi nding sites for blood group-related neoglycoconjugates in the range of N si milar to 10(6)-10(7)/cell with K-D-values in the muM range. Treatment of PM Ns (2 x 10(6) cells/ml) with PAA-probes (50 mug/ml) for 5 min did not activ ate the "respiratory burst". However, it led to suppression (range 20-70%) of H2O2 generation of cells in the presence of elicitors. In detail, the FM LP-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 s ignificantly VAA-mediated release of H2O2 from PMNs. In this case, interfer ence can take place already, at the stage of initial binding, especially fo r B- and H-epitopes, but less prominently for A- and SiaLe-epitopes. These results support the notion that PAA-immobilized histo-blood group oligosacc harides can serve as effector molecules with the ability to reduce the H2O2 -generation of PMNs, warranting further studies on the involved reaction pa thway. (C) 2001 Elsevier Science Ltd. All rights reserved.