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Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 21, 2008; 14(39): 6036-6043
Published online Oct 21, 2008. doi: 10.3748/wjg.14.6036
Decreased phagocytic activity of Kupffer cells in a rat nonalcoholic steatohepatitis model
Tatsuhiro Tsujimoto, Hideto Kawaratani, Toshiyuki Kitazawa, Toshiko Hirai, Hajime Ohishi, Mitsuteru Kitade, Hitoshi Yoshiji, Masahito Uemura, Hiroshi Fukui
Tatsuhiro Tsujimoto, Hideto Kawaratani, Toshiyuki Kitazawa, Mitsuteru Kitade, Hitoshi Yoshiji, Masahito Uemura, Hiroshi Fukui, Third Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan
Toshiko Hirai, Hajime Ohishi, Department of Endoscopy and Ultrasound, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan
Author contributions: Tsujimoto T and Fukui H designed the research project; Tsujimoto T, Kawaratani H, Kitazawa T and Kitade M contributed to the immunohistochemical staining; Tsujimoto T, Hirai T and Ohishi H contributed to contrast enhanced ultrasonography (CEUS) examination; Tsujimoto T, Kawaratani H, Yoshiji H and Uemura M analysed the data; and Tsujimoto T wrote the paper.
Supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, No. 19590784
Correspondence to: Tatsuhiro Tsujimoto, MD, PhD, Third Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. tat-tyan@xa2.so-net.ne.jp
Telephone: +81-744-223051 Fax: +81-744-247122
Received: June 20, 2008
Revised: September 16, 2008
Accepted: September 23, 2008
Published online: October 21, 2008
Abstract

AIM: To investigate Kupffer cell dynamics and phagocytic activity, using a rat nonalcoholic steatohepatitis (NASH) model.

METHODS: Male F344 rats were fed either a control diet or a choline-deficient L-amino acid-defined (CDAA) diet, followed by contrast enhanced ultrasonography (CEUS) using Levovist®. The uptake of latex beads by the Kupffer cells was determined by fluorescent microscopy. The status of the Kupffer cells was compared between the two groups, using the immunohistochemical staining technique.

RESULTS: After 4 or more wk of the CDAA diet, CEUS examination revealed a decrease in the signal intensity, 20 min after intravenous Levovist®. Fluorescent microscopic examination showed that the uptake of latex beads by the Kupffer cells was reduced at week 1 and 2 in the study group, compared with the controls, with no further reduction after 3 wk. Immunohistochemical staining revealed no significant difference in the Kupffer cell counts between the control group and the CDAA group.

CONCLUSION: CEUS examination using Levovist® demonstrated reduced contrast effect and phagocytic activity in the liver parenchymal phase, although the Kupffer cell numbers were unchanged, indicating reduced phagocytic function of the Kupffer cells in the rat NASH model. We believe that CEUS examination using Levovist® is a useful screening modality, which can detect NASH in fatty liver patients.

Keywords: Nonalcoholic steatohepatitis; Kupffer cells; Contrast enhanced ultrasonography; Levovist; Ultrasound contrast agent; Phagocytic activity