Cryptic sialic acid binding lectins on human blood leukocytes can be unmasked by sialidase treatment or cellular activation.
We recently reported that the sialic acid-specific binding sites of CD22 molecules on B cells are masked by endogenous ligands, and can be unmasked by sialidase treatment or cellular activation. Here, we show that many other human blood leukocyte types have endogenous sialic acid binding sites that can be unmasked by sialidase treatment. Truncation of sialic acid side chains on the soluble probes used for detection abolishes all binding, indicating the specificity of the interaction for the details of sialic acid structure. There is limited overlap between alpha2-6- and alpha2-3-sialic acid-specific binding sites, which are unmasked on monocytes, natural killer cells, a minority of mature T cells, neutrophils, and some cultured human leukemic cell lines. Activation with phorbol ester and calcium ionophore causes spontaneous exposure of some of the binding sites, occurring over a period of minutes on neutrophils and several hours on monocytes and U937 leukemia cells. Activation is accompanied by some evidence for desialylation of cell surface molecules. Thus, many human blood cells have specific binding sites for sialic acids, masked by endogenous sialylated ligands. Cellular activation can unmask these sites, possibly by the action of an endogenous sialidase. The nearly universal masking of such sites in unactivated blood cells could explain why many of these sialic acid-binding lectins have not been previously discovered. Similar considerations may apply to sialic acid binding lectins of other cell types and tissues.
Razi
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Glycobiology Program and Cancer Center, Divisions of Hematology-Oncology, and Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Varki
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A
D001665:Binding Sites; D019921:Biotinylation; D019337:Hematologic Neoplasms / Q000473:pathology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007785:Lactose / Q000031:analogs & derivatives / Q000378:metabolism; D037102:Lectins / Q000097:blood*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009439:Neuraminidase / Q000494:pharmacology*; D018375:Neutrophil Activation / Q000187:drug effects*; D012794:Sialic Acids / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007476:Ionophores; D037102:Lectins; D012794:Sialic Acids; C000020:N-acetylneuraminoyllactose; D015759:Ionomycin; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D007785:Lactose; D013755:Tetradecanoylphorbol Acetate