title: Role of apolipoprotein B100 and oxidized low-density lipoprotein in the monocyte tissue factor induction mediated by anti-β2 glycoprotein I antibodies.
abstract: OBJECTIVE
  The objective of this paper is to elucidate the not yet known plasma molecule candidates involved in the induction of tissue factor (TF) expression mediated by β2GPI-dependent anticardiolipin antibody (aCL/β2GPI) on monocytes.
  
  
  METHODS
  Human serum incubated with FLAG-β2GPI was applied for affinity chromatography with anti- FLAG antibody. Immunopurified proteins were analyzed by a liquid chromatography coupled with mass spectrometry (LC-MS). TF mRNA induced by the identified molecules on monocytes was also analyzed.
  
  
  RESULTS
  Apolipoprotein B100 (APOB) was the only identified serum molecule in the MS search. Oxidized LDL, containing APOB as well as ox-Lig1 (a known ligand of β2GPI), was revealed as a β2GPI-binding molecule in the immunoprecipitation assay. TF mRNA was markedly induced by oxidized LDL/β2GPI complexes with either WBCAL-1 (monoclonal aCL/β2GPI) or purified IgG from APS patients. The activities of lipoprotein-associated phospholipase A2, one of the component molecules of oxidized LDL, were significantly higher in serum from APS patients than in those from controls.
  
  
  CONCLUSIONS
  APOB (or oxidized LDL) was detected as a major β2GPI binding serum molecule by LC-MS search. Oxidized LDL/aCL/β2GPI complexes significantly induced TF expressions on monocytes. These data suggest that complexes of oxidized LDL and aCL/β2GPI may have a crucial role in the pathophysiology of APS.
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Otomo
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Amengual
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujieda
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Oku
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Horita
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Division of Proteomics, Multi-scale Research Center for Prevention of Medical Science, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Division of Proteomics, Multi-scale Research Center for Prevention of Medical Science, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: K I
authors.initials: KI
authors.lastname: Nakayama
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hatakeyama
authors.affiliation: Sapporo Medical Center NTT EC, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Koike
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan at3tat@med.hokudai.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Atsumi
mesh_terms: D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000097:blood*; D053299:Apolipoprotein B-100 / Q000097:blood*; D057809:HEK293 Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D051379:Mice; D000067996:RAW 264.7 Cells; D013925:Thromboplastin / Q000096:biosynthesis*; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: C569471:APOB protein, human; D017153:Antibodies, Anticardiolipin; D053299:Apolipoprotein B-100; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein; D013925:Thromboplastin
keywords: Apolipoprotein B100; anticardiolipin antibody; beta2-glycoprotein I; lipoprotein-associated phospholipase A2; oxidized LDL; tissue factor