title: Human alpha-fetoprotein binds to primary macrophages.
abstract: We have previously reported that alpha-fetoprotein (AFP) inhibits infection of human monocyte-derived macrophages (MDM) by R5-HIV-1 strains and that a peptide mimicking the clade B HIV-1 gp120 consensus V3 domain (V3Cs) binds to CCR5. We demonstrate here that AFP binds high- and low-affinity binding sites of MDM, characterized, respectively, by 5.15 and 100nM K(d) values. Heat denaturation or neuraminidase treatment of AFP inhibits this binding, suggesting the involvement of protein-protein and lectin-carbohydrate interactions. Moreover, AFP displaces V3Cs binding to MDM. In addition, MIP-1beta, the most specific CCR5 ligand, displaces AFP binding to MDM (IC(50)=4.3nM). Finally, we demonstrate that AFP binds to a ligand of HIV-gp120 V3Cs domain, CCR5, expressed by MDM and by HeLa cells expressing CCR5. Such binding is not observed in the presence of HeLa cells lacking CCR5. The present results provide strong evidence that AFP directly binds to CCR5 expressed by human primary macrophages and by transfected CCR5+ HeLa cells.
authors.affiliation: UPRES 3410, Biothérapies, Bénéfices et Risques, UFR-SMBH, Université Paris XIII, Bobigny et Hôpital Jean Verdier, Bondy 93017, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Atemezem
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mbemba
authors.forename: Renée
authors.initials: R
authors.lastname: Marfaing
authors.forename: Jenny
authors.initials: J
authors.lastname: Vaysse
authors.forename: Michel
authors.initials: M
authors.lastname: Pontet
authors.forename: Line
authors.initials: L
authors.lastname: Saffar
authors.forename: Nathalie
authors.initials: N
authors.lastname: Charnaux
authors.forename: Liliane
authors.initials: L
authors.lastname: Gattegno
mesh_terms: D001665:Binding Sites; D001667:Binding, Competitive; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology; D010455:Peptides / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D015699:HIV Envelope Protein gp120; D010455:Peptides; D019713:Receptors, CCR5; D000509:alpha-Fetoproteins