Characterization of CD33 as a new member of the sialoadhesin family of cellular interaction molecules.
CD33 is a member of the Ig superfamily that is restricted to cells of the myelomonocytic lineage but whose functions and binding properties are unknown. It shares sequence similarity with sialoadhesin, CD22, and the myelin-associated glycoprotein, which constitute the Sialoadhesin family of sialic acid-dependent cell adhesion molecules. In the present study, we show that CD33 is a fourth member of this family. As a model for sialic acid-dependent binding, human erythrocytes were derivatized with N-acetylneuraminic acid (NeuAc) in different linkages. A recombinant soluble form of CD33, Fc-CD33, bound red blood cells with a specificity similar to that of sialoadhesin, preferring NeuAc alpha 2,3Gal in N- and O-glycans over NeuAc alpha 2,6Gal in N-glycans. Fc-CD33 also bound selectively to the myeloid cell lines HL-60 and U937. However, CD33 was unable to mediate cell binding after transient expression in COS cells, despite high levels of surface expression. Pretreatment of the CD33-transfected cells with sialidase rendered them capable of mediating sialic acid-dependent binding. These results show that CD33 can function as a sialic acid-dependent cell adhesion molecule and that binding can be modulated by endogenous sialoglycoconjugates when CD33 is expressed in a plasma membrane.
Freeman
S D
SD
Molecular Haemopoiesis Laboratory, Imperial Cancer Research Fund (ICRF), University of Oxford, John Radcliffe Hospital, Headington, UK.
Kelm
S
S
Barber
E K
EK
Crocker
P R
PR
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000502:physiology*; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics; D004912:Erythrocytes / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007785:Lactose / Q000031:analogs & derivatives / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000145:classification* / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D019158:N-Acetylneuraminic Acid; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009439:Neuraminidase / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000145:classification* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D017385:Sequence Homology; D063267:Sialic Acid Binding Ig-like Lectin 1; D063268:Sialic Acid Binding Ig-like Lectin 3; D012794:Sialic Acids / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; D063268:Sialic Acid Binding Ig-like Lectin 3; D012794:Sialic Acids; C000020:N-acetylneuraminoyllactose; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D007785:Lactose