CHARACTERIZATION OF SIGLEC-5, A NOVEL GLYCOPROTEIN EXPRESSED ON MYELOID CELLS RELATED TO CD33

We describe the characterization of siglec-5 (sialic acid-binding Ig-l ike lectin-5), a novel transmembrane member of the immunoglobulin supe rfamily, highly related to the myeloid antigen, CD33. A full-length cD NA encoding siglec-5 was isolated from a human activated monocyte cDNA library. Sequencing predicted that siglec-5 contains four extracellul ar immunoglobulin-like domains, the N-terminal two of which are 57% id entical to the corresponding region of CD33. The cytoplasmic tail is a lso related to that of CD33, containing two tyrosine residues embodied in immunoreceptor tyrosine-based inhibitory motif-like motifs. The si glec-5 gene was shown to map to chromosome 19q13.41-43, closely linked to the CD33 gene. When siglec-5 was expressed on COS cells or as a re combinant protein fused to the Fc region of human IgG1, it was able to mediate sialic acid-dependent binding to human erythrocytes and solub le glycoconjugates; suggesting that it may be involved in cell-cell in teractions. By using specific antibodies, siglec-5 was found to have a n expression pattern distinct from that of CD33, being present at rela tively high levels on neutrophils but absent from leukemic cell lines representing early stages of myelomonocytic differentiation. Western b lot analysis of neutrophil lysates indicated that siglec-5 exists as a disulfide-linked dimer of approximately 140 kD. (C) 1998 by The Ameri can Society of Hematology.