Specific inhibition of human natural killer cell-mediated cytotoxicity by sialic acid and sialo-oligosaccharides

✍ Scribed by Johanna van Rinsum; Lou A. Smets; Henny van Rooy; Dirk H. van den Eijnden

• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: French
• Weight: 911 KB
• Volume: 38
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910380620

✦ Synopsis

We have tried to identify carbohydrate structures involved in recognition and/or lysis of K562 target cells by human natural killer (NK) cells. Inhibition studies were performed with mono-, di-and trisaccharides, and with glycopeptides and glycoproteins of known carbohydrate composition. When tested with various monosaccharides, lysis of K562 cells was inhibited only by N-acetylneuraminic acid (NeuAc). Di-and trisaccharides and glycopeptides containing NeuAc or Nglycolylneuraminic acid (NeuGc) all inhibited NK cellmediated lysis. Among the non-sialylated carbohydrates tested, only Gal@( I -+3)CalNAcol was effective. The inhibitory capacity of sialylated compounds appeared to be dependent on the linkage type of the sialic acid residue; carbohydrates containing or(2+6)linked sialic acids were more potent inhibitors than their (~(2'3) isomers. Also the sugar to which the sialic acid residue was attached was of importance, NeuAcor(Z-t6)GalNAcoI being more effective than NeuAcor(Z-t6)Gal@I +R (where R = glucose or oligosaccharide-peptide). Sialylated compounds and free sialic acid had minor or no effects on cell-mediated cytotoxicity by allo-sensitized cytotoxic T lymphocytes. The conjugation of target cells and NK effector cells was not inhibited by carbohydrates that effectively blocked the cytolytic response. These results may indicate that cell-surface carbohydrates containing or(2+6)-linked sialic acid are crucial structures in a post-binding event in NK-cell-mediated lysis.