title: Crucial role of impaired Kupffer cell phagocytosis on the decreased Sonazoid-enhanced echogenicity in a liver of a nonalchoholic steatohepatitis rat model.
abstract: OBJECTIVE
  To evaluate the dynamics of Kupffer cell (KC) phagocytosis by performing both in vivo and in vitro studies using Sonazoid (GE Healthcare, Oslo) in a rat nonalcoholic steatohepatitis (NASH) model.
  
  
  METHODS
  Contrast enhanced ultrasonography (CEUS) was performed on a rat NASH model induced by a methionine choline deficient diet (MCDD) and control rats, and Sonazoid was used to measure the signal intensity in the liver parenchyma. The uptake of Sonazoid by the KCs was observed by intravital microscopy. Their phagocytic capability was evaluated in vitro using isolated and cultured KCs. The uptake of fluorescein isothiocyanate (FITC)-labeled latex beads was observed and quantitatively analyzed by flow cytometry.
  
  
  RESULTS
  In the MCDD group, liver parenchymal enhancement was reduced 20 min after the Sonazoid injection. Microscopic observation of the isolated and cultured KCs revealed that the number of phagocytosed Sonazoid microbubbles was significantly decreased. Confocal laser scanning microscopic (CLSM) observation showed a decrease in the uptake of the latex beads. A decreased phagocytic capacity in the MCDD group was suggested by the quantitative analysis using flow cytometry, as well as by intravital microscopy.
  
  
  CONCLUSIONS
  CEUS with Sonazoid is a powerful evaluation tool to diagnose NASH from an early stage of the disease.
authors.affiliation: Division of Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo College of Medicine, Tokyo, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Yoshikawa
authors.forename: Hiroko
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authors.lastname: Iijima
authors.forename: Masaki
authors.initials: M
authors.lastname: Saito
authors.forename: Hironori
authors.initials: H
authors.lastname: Tanaka
authors.forename: Hiroyasu
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authors.lastname: Imanishi
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimoto
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Shizue
authors.initials: S
authors.lastname: Futatsugi-Yumikura
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Tohru
authors.initials: T
authors.lastname: Tsujimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishigami
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kudo
authors.forename: Shigeki
authors.initials: S
authors.lastname: Arii
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi