title: ABO blood group glycans modulate sialic acid recognition on erythrocytes.
abstract: ABH(O) blood group polymorphisms are based on well-known intraspecies variations in structures of neutral blood cell surface glycans in humans and other primates. Whereas natural antibodies against these glycans can act as barriers to blood transfusion and transplantation, the normal functions of this long-standing evolutionary polymorphism remain largely unknown. Although microbial interactions have been suggested as a selective force, direct binding of lethal pathogens to ABH antigens has not been reported. We show in this study that ABH antigens found on human erythrocytes modulate the specific interactions of 3 sialic acid-recognizing proteins (human Siglec-2, 1918SC influenza hemagglutinin, and Sambucus nigra agglutinin) with sialylated glycans on the same cell surface. Using specific glycosidases that convert A and B glycans to the underlying H(O) structure, we show ABH antigens stabilize sialylated glycan clusters on erythrocyte membranes uniquely for each blood type, generating differential interactions of the 3 sialic acid-binding proteins with erythrocytes from each blood type. We further show that by stabilizing such structures ABH antigens can also modulate sialic acid-mediated interaction of pathogens such as Plasmodium falciparum malarial parasite. Thus, ABH antigens can noncovalently alter the presentation of other cell surface glycans to cognate-binding proteins, without themselves being a direct ligand.
authors.affiliation: Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Cohen
authors.forename: Nancy
authors.initials: N
authors.lastname: Hurtado-Ziola
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001789:Blood Group Antigens / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000378:metabolism*; D005434:Flow Cytometry; D006388:Hemagglutinins / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000378:metabolism / Q000469:parasitology; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D037121:Plant Lectins / Q000378:metabolism; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D054788:Ribosome Inactivating Proteins / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000378:metabolism
chemical_list: D000017:ABO Blood-Group System; D001789:Blood Group Antigens; D006388:Hemagglutinins; D037121:Plant Lectins; D011134:Polysaccharides; C050600:Sambucus nigra lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D054788:Ribosome Inactivating Proteins; D019158:N-Acetylneuraminic Acid
references.citation: Cell. 2005 Jul 29;122(2):183-93
references.pmid: 16051144
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12819-24
references.pmid: 16126901
references.citation: J Biol Chem. 1989 Dec 5;264(34):20159-62
references.pmid: 2584211
references.citation: J Biol Chem. 1991 Sep 15;266(26):17552-8
references.pmid: 1894638
references.citation: J Biol Chem. 2000 Mar 24;275(12):8633-40
references.pmid: 10722703
references.citation: J Virol. 2005 Jun;79(11):6714-22
references.pmid: 15890909
references.citation: J Neurol Neurosurg Psychiatry. 2008 Oct;79(10):1148-52
references.pmid: 18339728
references.citation: Biochem J. 2000 Aug 15;350 Pt 1:53-60
references.pmid: 10926825
references.citation: Methods Mol Biol. 2007;398:245-61
references.pmid: 18214385
references.citation: Nat Biotechnol. 2007 Apr;25(4):454-64
references.pmid: 17401360
references.citation: Arch Biochem Biophys. 2004 Sep 15;429(2):145-53
references.pmid: 15313217
references.citation: FEBS Lett. 2003 Jan 16;534(1-3):185-9
references.pmid: 12527384
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):18987-91
references.pmid: 17142315
references.citation: Methods Enzymol. 2000;312:447-58
references.pmid: 11070893
references.citation: Blood. 1990 Aug 15;76(4):842-8
references.pmid: 2383660
references.citation: Hum Genet. 2008 Sep;124(2):123-35
references.pmid: 18629539
references.citation: J Biol Chem. 2003 Nov 28;278(48):48245-50
references.pmid: 14500706
references.citation: Biochim Biophys Acta. 2001 Feb 16;1525(1-2):58-69
references.pmid: 11342254
references.citation: Tissue Antigens. 2006 Dec;68(6):459-66
references.pmid: 17176435
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17471-6
references.pmid: 17959777
references.citation: Science. 2004 Jul 23;305(5683):519-22
references.pmid: 15273394
references.citation: Histochem Cell Biol. 2006 May;125(5):451-6
references.pmid: 16284775
references.citation: Blood. 2007 Oct 1;110(7):2250-8
references.pmid: 17502454
references.citation: Am J Hematol. 1980;9(4):381-9
references.pmid: 7211833
references.citation: Glycoconj J. 1997 Feb;14(2):159-73
references.pmid: 9111133
references.citation: Mol Biol Evol. 1997 Apr;14(4):399-411
references.pmid: 9100370
references.citation: Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7390-7
references.pmid: 7519775
references.citation: J Biol Chem. 1999 Aug 6;274(32):22729-38
references.pmid: 10428856
references.citation: Cell. 2006 Feb 24;124(4):755-66
references.pmid: 16497586
references.citation: Biophys J. 1995 May;68(5):1881-7
references.pmid: 7612830
references.citation: Glycobiology. 2009 Jul;19(7):789-96
references.pmid: 19349623
references.citation: J Biol Chem. 1993 Apr 5;268(10):7019-27
references.pmid: 8463235
references.citation: J Clin Invest. 1994 Jan;93(1):121-30
references.pmid: 8282779
references.citation: J Mol Biol. 2006 Feb 3;355(5):1143-55
references.pmid: 16343533
references.citation: Trends Parasitol. 2006 Apr;22(4):143-5
references.pmid: 16497558
references.citation: Br J Haematol. 2006 Nov;135(3):395-404
references.pmid: 16989660
references.citation: J Immunogenet. 1990 Aug-Oct;17(4-5):219-25
references.pmid: 2093725
references.citation: J Biol Chem. 1987 Feb 5;262(4):1596-601
references.pmid: 3805045
references.citation: Nature. 2007 Apr 26;446(7139):1023-9
references.pmid: 17460663
references.citation: Infect Immun. 2007 Jun;75(6):3014-20
references.pmid: 17438038
references.citation: Proc Biol Sci. 2004 May 22;271(1543):1065-72
references.pmid: 15293861
references.citation: Nature. 1990 May 17;345(6272):229-33
references.pmid: 2333095
references.citation: Eur J Biochem. 1995 Dec 1;234(2):616-25
references.pmid: 8536711
references.citation: Nat Rev Immunol. 2007 Apr;7(4):255-66
references.pmid: 17380156