Siglec-1

Siglec-1 (sialoadhesin, CD169, SN) is the founding member of the Siglec family and the only one lacking cytoplasmic signaling motifs, functioning as a pure sialic acid-binding adhesion receptor. Siglec-1 is a 185-kDa type I transmembrane glycoprotein with an extraordinary 17 extracellular Ig-like domains (one V-set sialic acid-binding domain and 16 C2-set domains) creating a molecule long enough to extend beyond the glycocalyx and mediate intercellular interactions. It is specifically expressed on tissue macrophages-hematopoietic spleen marginal zone metallophilic macrophages, lymph node subcapsular sinus macrophages, bone marrow macrophages and inflammatory macrophages. Siglec-1 preferentially binds α2,3-sialylated glycans, mediating macrophage interactions with lymphocytes, granulocytes and pathogens (including sialylated bacteria like Campylobacter jejuni). It captures pathogens and tumor-derived exosomes for antigen presentation, facilitates HIV trans-infection of T cells by macrophages, and marks inflammatory macrophages in atherosclerosis, multiple sclerosis and Guillain-Barré syndrome, making CD169 a macrophage activation biomarker and therapeutic target.