Impact of polysialylated CD56 on natural killer cell cytotoxicity

Moebius, Jeannette M.; Widera, Darius; Schmitz, Juergen; Kaltschmidt, Christian; Piechaczek, Christoph

doi:10.1186/1471-2172-8-13

Cited by 30 publications

(32 citation statements)

References 20 publications

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“…Herein we demonstrated the presence of polySia on human NK cells and its absence on other immune subsets, a finding that is in accord with two earlier reports (26,27). NK cells up-regulated the expression of polySia and its scaffold NCAM upon activation by IL-2 treatment.…”

Section: Discussionsupporting

confidence: 92%

Polysialic Acid, a Glycan with Highly Restricted Expression, Is Found on Human and Murine Leukocytes and Modulates Immune Responses

Drake¹,

Nathan²,

Stock³

et al. 2008

The Journal of Immunology

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Polysialic acid (polySia) is a large glycan with restricted expression, typically found attached to the protein scaffold neural cell adhesion molecule (NCAM). PolySia is best known for its proposed role in modulating neuronal development. Its presence and potential functions outside the nervous systems are essentially unexplored. Herein we show the expression of polySia on hematopoietic progenitor cells, and demonstrate a role for this glycan in immune response using both acute inflammatory and tumor models. Specifically, we found that human NK cells modulate expression of NCAM and the degree of polymerization of its polySia glycans according to activation state. This contrasts with the mouse, where polySia and NCAM expression are restricted to multipotent hematopoietic progenitors and cells developing along a myeloid lineage. Sialyltransferase 8Sia IV−/− mice, which lacked polySia expression in the immune compartment, demonstrated an increased contact hypersensitivity response and decreased control of tumor growth as compared with wild-type animals. This is the first demonstration of polySia expression and regulation on myeloid cells, and the results in animal models suggest a role for polySia in immune regulation.

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Section: Discussionsupporting

confidence: 92%

Polysialic Acid, a Glycan with Highly Restricted Expression, Is Found on Human and Murine Leukocytes and Modulates Immune Responses

Drake¹,

Nathan²,

Stock³

et al. 2008

The Journal of Immunology

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“…Very little PSA has been found in nonneural tissues, with the exception of immune cells. PSA was found on the cell surface of natural killer cells (Moebius et al, 2007). PSA was also associated with glycoproteins expressed on dendritic cells (Curreli et al, 2007).…”

Section: Discussionmentioning

confidence: 98%

Alleviation of Neurotoxicity by Microglial Human Siglec-11

Wang¹,

Neumann²

2010

J. Neurosci.

161

132

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“…The a2,8-linked polysialic acid is also found in vertebrates, where it is primarily found as a posttranslational modification of NCAM [4,58]. It was also described as a major glycan structure of the CD36 scavenger receptor in human milk, the a-subunit of the voltage-gated sodium channel in rat brain, neuropilin-2 on maturating human dendritic cells, and recently identified as posttranslational modification of SynCAM 1 in mouse brain [2,3,[59][60][61][62][63]. Polysialic acid has been ascribed important roles in neural development, cell differentiation and plasticity [5].…”

Section: Bacteriophagesmentioning

confidence: 99%

“…It has been suggested that this polysialylation is important for neonatal development in terms of protection and nutrition. EndoNF and monoclonal antibodies mAb 12E3 (IgM) recognizing oligo/ [61,185,186]. Neural polysialic acid participates in migration, cytokine response, and cell contact-dependent differentiation.…”

Section: Other Applications Of Active Endosialidasementioning

confidence: 99%

Endosialidases: Versatile Tools for the Study of Polysialic Acid

Jakobsson

Schwarzer

Jokilammi

et al. 2012

Topics in Current Chemistry

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Polysialic acid is an α2,8-linked N-acetylneuraminic acid polymer found on the surface of both bacterial and eukaryotic cells. Endosialidases are bacteriophage-borne glycosyl hydrolases that specifically cleave polysialic acid. The crystal structure of an endosialidase reveals a trimeric mushroom-shaped molecule which, in addition to the active site, harbors two additional polysialic acid binding sites. Folding of the protein crucially depends on an intramolecular C-terminal chaperone domain that is proteolytically released in an intramolecular reaction. Based on structural data and previous considerations, an updated catalytic mechanism is discussed. Endosialidases degrade polysialic acid in a processive mode of action, and a model for its mechanism is suggested. The review summarizes the structural and biochemical elucidations of the last decade and the importance of endosialidases in biochemical and medical applications. Active endosialidases are important tools in studies on the biological roles of polysialic acid, such as the pathogenesis of septicemia and meningitis by polysialic acid-encapsulated bacteria, or its role as a modulator of the adhesion and interactions of neural and other cells. Endosialidase mutants that have lost their polysialic acid cleaving activity while retaining their polysialic acid binding capability have been fused to green fluorescent protein to provide an efficient tool for the specific detection of polysialic acid.

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Impact of polysialylated CD56 on natural killer cell cytotoxicity

Abstract: Background: Siglec-7, a sialic acid binding inhibitory receptor expressed by NK cells is masked in vivo by a so far unknown ligand. It shows a strong binding prevalence for α-2,8-linked disialic acids in vitro.

Cited by 30 publications

References 20 publications

Polysialic Acid, a Glycan with Highly Restricted Expression, Is Found on Human and Murine Leukocytes and Modulates Immune Responses

Polysialic Acid, a Glycan with Highly Restricted Expression, Is Found on Human and Murine Leukocytes and Modulates Immune Responses

Alleviation of Neurotoxicity by Microglial Human Siglec-11

Endosialidases: Versatile Tools for the Study of Polysialic Acid

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