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      Diversity in cell surface sialic acid presentations: implications for biology and disease

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          Abstract

          Sialic acids (Sias) are typically found as terminal monosaccharides attached to cell surface glycoconjugates. They play many important roles in many physiological and pathological processes, including microbe binding that leads to infections, regulation of the immune response, the progression and spread of human malignancies and in certain aspects of human evolution. This review will provide some examples of these diverse roles of Sias and briefly address immunohistochemical approaches to their detection.

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          Most cited references 46

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          Avian flu: influenza virus receptors in the human airway.

          Although more than 100 people have been infected by H5N1 influenza A viruses, human-to-human transmission is rare. What are the molecular barriers limiting human-to-human transmission? Here we demonstrate an anatomical difference in the distribution in the human airway of the different binding molecules preferred by the avian and human influenza viruses. The respective molecules are sialic acid linked to galactose by an alpha-2,3 linkage (SAalpha2,3Gal) and by an alpha-2,6 linkage (SAalpha2,6Gal). Our findings may provide a rational explanation for why H5N1 viruses at present rarely infect and spread between humans although they can replicate efficiently in the lungs.
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            Glycan-based interactions involving vertebrate sialic-acid-recognizing proteins.

             Ajit Varki (2007)
            All cells in nature are covered by a dense and complex array of carbohydrates. Given their prominence on cell surfaces, it is not surprising that these glycans mediate and/or modulate many cellular interactions. Proteins that bind sialic acid, a sugar that is found on the surface of the cell and on secreted proteins in vertebrates, are involved in a broad range of biological processes, including intercellular adhesion, signalling and microbial attachment. Studying the roles of such proteins in vertebrates has improved our understanding of normal physiology, disease and human evolution.
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              Human embryonic stem cells express an immunogenic nonhuman sialic acid.

              Human embryonic stem cells (HESC) can potentially generate every body cell type, making them excellent candidates for cell- and tissue-replacement therapies. HESC are typically cultured with animal-derived 'serum replacements' on mouse feeder layers. Both of these are sources of the nonhuman sialic acid Neu5Gc, against which many humans have circulating antibodies. Both HESC and derived embryoid bodies metabolically incorporate substantial amounts of Neu5Gc under standard conditions. Exposure to human sera with antibodies specific for Neu5Gc resulted in binding of immunoglobulin and deposition of complement, which would lead to cell killing in vivo. Levels of Neu5Gc on HESC and embryoid bodies dropped after culture in heat-inactivated anti-Neu5Gc antibody-negative human serum, reducing binding of antibodies and complement from high-titer sera, while allowing maintenance of the undifferentiated state. Complete elimination of Neu5Gc would be likely to require using human serum with human feeder layers, ideally starting with fresh HESC that have never been exposed to animal products.
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                Author and article information

                Contributors
                VARKIADHIN@UCSD.EDU
                Journal
                Lab Invest
                Lab. Invest
                Laboratory Investigation; a Journal of Technical Methods and Pathology
                Nature Publishing Group US (New York )
                0023-6837
                1530-0307
                16 July 2007
                2007
                : 87
                : 9
                : 851-857
                Affiliations
                [1 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Pathology, , Glycobiology Research and Training Center, University of California at San Diego, ; La Jolla, CA USA
                [2 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Medicine, , University of California at San Diego, ; La Jolla, CA USA
                [3 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Cellular and Molecular Medicine, , University of California at San Diego, ; La Jolla, CA USA
                Article
                BF3700656
                10.1038/labinvest.3700656
                7100186
                17632542
                15628c01-1edd-41af-afd1-429b242c4c4f
                © United States and Canadian Academy of Pathology, Inc. 2007

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                © United States & Canadian Academy of Pathology 2007

                Pathology

                sialic acid, glycobiology, siglec, glycomics

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