Crucial role of impaired Kupffer cell phagocytosis on the decreased Sonazoid-enhanced echogenicity in a liver of a nonalchoholic steatohepatitis rat model.
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.
Yoshikawa
Shohei
S
Division of Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo College of Medicine, Tokyo, Japan.
Iijima
Hiroko
H
Saito
Masaki
M
Tanaka
Hironori
H
Imanishi
Hiroyasu
H
Yoshimoto
Naoki
N
Yoshimoto
Tomohiro
T
Futatsugi-Yumikura
Shizue
S
Nakanishi
Kenji
K
Tsujimura
Tohru
T
Nishigami
Takashi
T
Kudo
Atsushi
A
Arii
Shigeki
S
Nishiguchi
Shuhei
S