title: Plasma anti-α-galactoside antibody mediates lipoprotein(a) binding to macrophages.
abstract: Lipoprotein (a) [Lp(a)] is the dominant lipid in atherosclerotic plaques though it is much less numerous than LDL or HDL in circulation. Molecular mechanism of selective uptake of Lp(a) into macrophages is unclear. Lp(a) was reported to form circulating immune complexes with the IgG-dominated plasma anti-α-galactoside antibody (anti-Gal) using the serine- and threonine-rich peptide sequences ( STPS) on its apo(a) subunit as surrogate ligand but left the other binding site of antibody free. We examined if these monovalent immune complexes could bind to smaller STPS-containing molecules on macrophage surface. Using placental membrane O-glycosylated proteins (PMOP) isolated by lectin affinity chromatography as model it was shown that human cell surface glycoproteins were small enough to occupy both binding sites of anti-Gal since they increased the fluorescence of FITC label at Fc part of anti-Gal and inhibited binding of anti-Gal and Griffonia simplicifolia lectin of similar specificity to immobilized ligands. Pre-incubation with anti-Gal facilitated Lp(a) attachment to macrophages unless anti-Gal-specific sugar was present. Anti-Gal-mediated attachment of apo(a) to macrophages increased with the number of apo(a) subunits. Further, anti-Gal-mediated binding of the same sample of apo(a) increased with the specific activity of anti-Gal sample. Finally binding of anti-Gal and anti-Gal-apo(a) complex to PMOP and macrophages respectively was mostly inhibited by LDL suggesting STPS as major anti-Gal epitopes on the cell surface. Results indicated that circulating Lp(a)-anti-Gal immune complexes anchor on macrophages using STPS-bearing cell surface glycoproteins as ligands and offer a pathway for Lp(a) sequestration into macrophages.
authors.affiliation: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, India.
authors.forename: Binu
authors.initials: B
authors.lastname: Sheela
authors.affiliation: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, India.
authors.forename: Genu
authors.initials: G
authors.lastname: George
authors.affiliation: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, India.
authors.forename: Geetha
authors.initials: G
authors.lastname: Mandagini
authors.affiliation: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, India. psappu52@gmail.com.
authors.forename: Padinjaradath S
authors.initials: PS
authors.lastname: Appukuttan
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D005697:Galactosides / Q000037:antagonists & inhibitors*; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D037121:Plant Lectins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000906:Antibodies; D005697:Galactosides; C045475:Griffonia simplicifolia lectins; D017270:Lipoprotein(a); D037121:Plant Lectins
keywords: Anti-α-galactoside antibody; Lipoprotein(a); Macrophage; Serine-and threonine-rich peptide sequences