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Sialoadhesin (Sn) is an atypical siglec, due to the presence of an unusually large number of Ig domains (17) and the absence of tyrosine-based intracellular signaling motifs. Sn prefers NeuNAc in α2,3-linkage over α2,6 and α2,8 linkages but does not recognize NeuGc or NeuAc9Ac. Sn is expressed uniquely by macrophage subsets in vivo and the 17 Ig domains are thought to be important for its ability to mediate sialic acid-dependent adhesive functions. This contrasts with most other siglecs which are much shorter and masked by cis binding to co-expressed sialic acids.


CFG Participating Investigators contributing to the understanding of this paradigm

CFG Participating Investigators (PIs) contributing to the understanding of Sn include: Paul Crocker, Peter Delputte, Soerge Kelm, Ajit Varki

Progress toward understanding this GBP paradigm

This section documents what is currently known about sialoadhesin, its carbohydrate ligand(s), and how they interact to mediate cell communication. Further information can be found in the GBP Molecule Page for human and mouse sialoadhesin (a.k.a. Siglec-1) in the CFG database.

Carbohydrate ligands


Sn is a fairly promiscuous receptor, with a preference for Siaα2-3Gal over Siaα2-6Gal terminated glycans. Sn has a strict preference for Neu5Ac over Neu5Gc and Neu5Ac9Ac. In pull-down experiments using Sn-Fc constructs, mucin-like proteins with multiple O-linked glycans seem to be preferred (eg CD43, Muc-1), but whether these represent preferred counterreceptors during cell-cell interactions between Sn+ macrophages and other cells is unknown

Cellular expression of GBP and ligands

Sn is expressed exclusively by cells of the mononuclear phagocyte lineage, including in some cases myeloid dendritic cells as well as classic macrophages. It is expressed constitutively by many tissue macrophages, particularly those in primary and secondary lymphoid organs and may play a role in antigen capture and tolerance. Sn can also be induced on macrophages by IFN-α or agents that induce expression of IFN-α such as LPS or poly-I:C. Ligands for Sn are regulated via expression of sialyltransferases and are found on many cells of the body. Surveys of haemopoietic targets have identified granulocytes as being rich in Sn ligands but the functional significance of this is unclear at present.

Biosynthesis of ligands


Biological roles of GBP-ligand interaction

Sn contributes to proinflammatory immune responses in a variety of autoimmune diseases[1][2], and this may be due to suppression of Treg expansion as demonstrated in experimental allergic encephalomyelitis, a model for multiple sclerosis[3]. Sn has also been shown to function as a macrophage receptor for the porcine arterivirus[4] and can also promote macrophage uptake of sialylated bacteria such as Neisseria meningitidis[5].

CFG resources used in investigations

The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for sialoadhesin.

Glycan profiling

Glycogene microarray

Knockout mouse lines

Glycan array

The CFG glycan array has been probed with both murine and porcine Sn constructs, but no positive signals were obtained (click here), likely due to the low affinity of Sn for sialylated oligosaccharides.

Related GBPs



  1. Jiang, H. R. et al. Sialoadhesin promotes the inflammatory response in experimental autoimmune uveoretinitis. J Immunol 177, 2258-2264 (2006).
  2. Ip, C. W., Kroner, A., Crocker, P. R., Nave, K. A. & Martini, R. Sialoadhesin deficiency ameliorates myelin degeneration and axonopathic changes in the CNS of PLP overexpressing mice. Neurobiol Dis 25, 105-111 (2007).
  3. Wu, C. et al. Sialoadhesin-positive macrophages bind regulatory T cells, negatively controlling their expansion and autoimmune disease progression. J Immunol 182, 6508-6516 (2009).
  4. Delputte, P. L. et al. Porcine arterivirus attachment to the macrophage-specific receptor sialoadhesin is dependent on the sialic acid-binding activity of the N-terminal immunoglobulin domain of sialoadhesin. J Virol 81, 9546-9550 (2007).
  5. Jones, C., Virji, M. & Crocker, P. R. Recognition of sialylated meningococcal lipopolysaccharide by siglecs expressed on myeloid cells leads to enhanced bacterial uptake. Mol Microbiol 49, 1213-1225 (2003).


The CFG is grateful to the following PIs for their contributions to this wiki page: Paul Crocker, James Paulson

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