Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Human Siglec-5 is a sialic acid binding immunoglobulin (Ig)-like lectin (Siglec), comprising one N-terminal IgV-SET domain followed by three IgC2-SET domains, and a cytoplasmic domain with ITIM and SAP motifs which regulate cell signalling. We report the differential distribution of hSiglec-5 on neutrophil and macrophage subsets in tissues using monoclonal antibodies, 1A5 and 2H8, which require the first IgC2-SET domain for binding. Interestingly, hSiglec-5 was especially prominent on macrophages in reactive lymph nodes. We have identified four isoforms of hSiglec-5 possessing three (hSiglec-5-3L and -3C) or four (hSiglec-5-4L and -4S) extracellular domains linked to long (hSiglec-5-3L and -4L) or short (hSiglec-5-4S) cytoplasmic tails or existing as a soluble isoform (hSiglec-5-3C). hSiglec-5-4L has the broadest tissue distribution, being detected in adult spleen, thymus, lymph node, peripheral blood leucocytes and bone marrow, and in fetal lung and liver. A soluble Fc chimaeric protein containing the hSiglec-5-4L extracellular domain binds in a sialic acid-dependent manner to glycophorin A on human erythrocytes and to alpha2-3- and alpha2-6-sialyllactose moieties. Domain deletion mutants of hSiglec-5(D1-4)-Fc reveal that the first three IgC2-SET domains are required for optimal binding, with adhesion being abolished if the first IgC2-SET domain is deleted. This indicates that each hSiglec-5 isoform will interact with sialic acid ligands and provides the first step towards defining structure-function relationships of hSiglec-5 isoforms.

Original publication




Journal article


Br J Haematol

Publication Date





221 - 238


Amino Acid Sequence, Antibodies, Monoclonal, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Chimera, Enzyme-Linked Immunosorbent Assay, Epitopes, Erythrocytes, Hematopoietic Stem Cells, Humans, Lectins, Macrophages, Molecular Sequence Data, Monocytes, N-Acetylneuraminic Acid, Neutrophils, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction