title: Super paramagnetic iron oxide MRI shows defective Kupffer cell uptake function in non-alcoholic fatty liver disease.
abstract: BACKGROUND
  The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is incompletely understood. Kupffer cells (KCs), phagocytic liver-resident macrophages, provide a protective barrier against egress of endotoxin from the portal to the systemic circulation. It is not known if KC phagocytic function is impaired in NAFLD. Super-paramagnetic iron oxide (SPIO) magnetic resonance imaging is a comparative technology dependent on KC phagocytic function.
  
  
  OBJECTIVE
  To evaluate KC uptake function, in patients and experimental animals with NAFLD, using SPIO.
  
  
  METHODS
  Abdominal CT and histological examination of liver biopsy specimens were used to estimate the degree of steatosis in patients with NAFLD and controls with chronic hepatitis C. SPIO-MRI was then performed in all patients. Normal rats fed a methionine-choline-deficient diet to induce non-alcoholic steatohepatitis (NASH), the more severe stage of NAFLD, and obese, insulin resistant, Zucker fa/fa rats with steatohepatitis, were also studied with SPIO-MRI and analysed for hepatic uptake of fluorescent microbeads. Immunohistochemical analysis evaluated the numbers of KCs in patients and rat livers.
  
  
  RESULTS
  Relative signal enhancement (RSE), inversely proportional to KC function, was higher in patients with NAFLD than in controls and with the degree of steatosis on CT. RSE also positively correlated with the degree of steatosis on histology and was similarly higher in rats with induced severe NAFLD (NASH). On immunohistochemistry, defective phagocytic function was the result of reduced phagocytic uptake and not due to reduced KC numbers in rats or patients with NAFLD.
  
  
  CONCLUSIONS
  KC uptake function is significantly impaired in patients with NAFLD and experimental animals with NASH, worsens with the degree of steatosis and is not due to a reduction of KC numbers.
authors.affiliation: Department of Radiology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Asanuma
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ono
authors.forename: Kei
authors.initials: K
authors.lastname: Kubota
authors.forename: Akira
authors.initials: A
authors.lastname: Hirose
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Toshiji
authors.initials: T
authors.lastname: Saibara
authors.forename: Osamu
authors.initials: O
authors.lastname: Inanami
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Enzan
authors.forename: Saburo
authors.initials: S
authors.lastname: Onishi
authors.forename: Mikinori
authors.initials: M
authors.lastname: Kuwabara
authors.forename: Jude A
authors.initials: JA
authors.lastname: Oben
mesh_terms: D000818:Animals; D002452:Cell Count; D003287:Contrast Media; D003911:Dextrans; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D052203:Ferrosoferric Oxide; D006801:Humans; D007728:Kupffer Cells / Q000502:physiology*; D008102:Liver Circulation / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles; D008297:Male; D008833:Microcirculation / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D012720:Severity of Illness Index
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides; D052203:Ferrosoferric Oxide