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Infection and Immunity, March 1999, p. 1018-1024, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Role of Nitric Oxide in Lipopolysaccharide-Induced Hepatic Injury in D-Galactosamine-Sensitized Mice as an Experimental Endotoxic Shock Model

Akiko Morikawa, Yutaka Kato, Tuyoshi Sugiyama, Naoki Koide, Dipshika Chakravortty, Tomoaki Yoshida, and Takashi Yokochi*

Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University, Nagakute, Aichi 480-1195, Japan

Received 29 July 1998/Returned for modification 15 October 1998/Accepted 4 December 1998

The role of nitric oxide (NO) in lipopolysaccharide (LPS)-induced hepatic injury was studied in D-galactosamine (D-GalN)-sensitized mice. The inducible isoform of NO synthase (iNOS) was immunohistochemically detected on hepatocytes around blood vessels in livers of mice injected with D-GalN and LPS not on hepatocytes in mice injected with D-GalN or LPS alone, although mRNA for iNOS was found in those mice. Nitrotyrosine (NT) was also found in livers of mice injected with D-GalN and LPS. The localization of NT was consistent with that of iNOS, and the time courses of NT and iNOS expression were almost the same. Expression of iNOS and NT was detected exclusively in the hepatic lesions of mice injected with D-GalN and LPS. Anti-tumor necrosis factor alpha neutralizing antibody inhibited iNOS and NT expression and hepatic injury. The results suggested that NO from iNOS may play a role in LPS-induced hepatic injury on D-GalN-sensitized mice as an experimental endotoxic shock model.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan. Phone: 81-561-62-3311, ext. 2269. Fax: 81-561-63-9187. E-mail: yokochi{at}amugw.aichi-med-u.ac.jp.


Infection and Immunity, March 1999, p. 1018-1024, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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