Sialoadhesin - a macrophage-restricted marker of immunoregulation and inflammation

Abstract

Sialoadhesin (Sn, also known as Siglec-1 and CD169) is a macrophage-restricted cell surface receptor that is conserved across mammals. Sn is a member of the sialic acid-binding IgG-like lectin (Siglec) family of proteins characterized by affinity to specifically sialylated ligands, and under normal conditions is expressed on subsets of macrophages in secondary lymphoid tissues, such as lymph node and spleen. However, Sn-positive macrophages can also be found in a variety of pathological conditions, including (autoimmune) inflammatory infiltrates and tumours. Sn has been shown to contribute to sialylated pathogen uptake, antigen presentation and lymphocyte proliferation, and to influence both immunity and tolerance. This review presents Sn as a macrophage-specific marker of inflammation and immunoregulation with the potential to becoming an important biomarker for immunologically active macrophages and a target for therapy.

Figure 1

Comparison of the distribution of sialoadhesin‐positive macrophages (Sn⁺ Mφ) in the splenic microenvironment. A framework of reticular fibroblasts (blue) forms the basis of the marginal zone and is continuous with the reticular fibroblasts in the red pulp and the sinus‐lining cells (green) of the marginal sinus. In all species, Sn⁺ Mφ (red) are observed as a line of cells at the internal border of the white pulp (the so‐called marginal metallophilic Mφ (MMM). In rodents, the white pulp is separated from the marginal zone (MZ) by a marginal sinus, and in the case of the rat spleen, Sn⁺ Mφ are observed in the marginal zone. In humans, the marginal zone is absent of Sn⁺ Mφ, but the unique structure known as the perifollicular zone contains Sn⁺ Mφ both sporadically and clustered around arteriolae (known as periarteriolar‐associated Mφ (PAM). Figure adapted from ref. .