title: Lipoprotein-X in cholestatic patients causes xanthomas and promotes foam cell formation in human macrophages.
abstract: Lipoprotein-X (Lp-X) is an abnormal phospholipid-rich lipoprotein found in patients with cholestatic liver disease. Some patients exhibit skin xanthomas and severe hyperlipidemia.
  
  
  
  We investigated whether Lp-X induces foam cell formation in human-derived macrophages.
  
  
  
  To compare the atherogenic properties of Lp-X and modified LDL, we isolated Lp-X from 2 patients who had drug-induced cholestasis and xanthoma striata in the interphalangeal folds. We prepared oxidized LDL and acetylated LDL from healthy volunteers for the positive control experiments.
  
  
  
  When human monocyte-derived macrophages were incubated with these lipoproteins, the isolated Lp-X induced more prominent lipid accumulation than oxidized LDL or acetylated LDL. One case underwent liver biopsy, with the bile ducts showing marked damage, fulfilling the criteria for vanishing bile duct syndrome. The other case was clinically diagnosed as drug-induced hypersensitivity syndrome. In both cases, Lp-X levels decreased markedly and the xanthomas disappeared completely after the improvement of cholestasis.
  
  
  
  This study indicates that Lp-X induces foam cell formation in human-derived macrophages. Our findings strongly suggest that persistently elevated Lp-X may cause xanthomas.
authors.affiliation: Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Luka
authors.initials: L
authors.lastname: Suzuki
authors.affiliation: Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirayama
authors.affiliation: Department of General Thoracic Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Fukui
authors.affiliation: Division of Anti-Aging and Vascular Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Division of Pathology, Department of Clinical Laboratory Sciences, Nitobe Bunka College, Tokyo, Japan.
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Hiroi
authors.affiliation: Tokorozawa Heart Center, Tokorozawa, Saitama, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ayaori
authors.affiliation: Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Niigata, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.affiliation: Analytical Laboratory Chemistry, Division of Biomedical Laboratory Sciences, Department of Moleculo-genetic Sciences, Tokyo Medical and Dental University Graduate School of Health Care Sciences, Tokyo, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tozuka
authors.affiliation: Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
authors.affiliation: Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: tmiida@juntendo.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miida
mesh_terms: D000328:Adult; D002779:Cholestasis / Q000150:complications / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005487:Foam Cells / Q000166:cytology*; D006801:Humans; D008073:Lipoprotein-X / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D014973:Xanthomatosis / Q000150:complications*; D055815:Young Adult
chemical_list: D008073:Lipoprotein-X
keywords: Cholestasis; Dyslipidemia; Lipoprotein-X; Macrophage; Oxidized LDL; Scavenger receptor; Xanthoma