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Infection and Immunity, August 1999, p. 4112-4118, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Expression of Fas and Fas Ligand on Mouse Renal Tubular Epithelial Cells in the Generalized Shwartzman Reaction and Its Relationship to Apoptosis

Naoki Koide,* Kayo Narita, Yutaka Kato, Tsuyoshi Sugiyama, Dipshikha Chakravortty, Akiko Morikawa, Tomoaki Yoshida, and Takashi Yokochi

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

Received 18 February 1999/Returned for modification 29 March 1999/Accepted 20 May 1999

Previously we reported that the consecutive injection of lipopolysaccharide (LPS) into LPS-sensitized mice for the generalized Shwartzman reaction (GSR) appeared to induce the injury of renal tubular epithelial cells via apoptosis. The aim of this study was to characterize the mechanism of renal tubular epithelial cell injury in GSR. The expression of Fas and Fas ligand was immunohistochemically detected on renal tubular epithelial cells from GSR-induced mice, although neither Fas nor Fas ligand was found in cells from untreated control mice or in cells from mice receiving a single injection of LPS. GSR-induced renal tubular epithelial cell injury was produced in neither Fas-negative MRL-lpr/lpr mice nor Fas ligand-negative MRL-gld/gld mice. The administration of anti-gamma interferon antibody together with a preparative injection of LPS prevented the expression of Fas and Fas ligand and the apoptosis of renal tubular epithelial cells. A provocative injection of tumor necrosis factor alpha into LPS-sensitized mice augmented Fas and Fas ligand expression and the apoptosis of renal tubular epithelial cells. The administration of tumor necrosis factor alpha to interleukin-12-sensitized mice resulted in Fas and Fas ligand expression and the apoptosis. Sensitization with interleukin-12 together with anti-gamma interferon antibody did not cause the apoptosis of renal tubular epithelial cells. It was suggested that the Fas/Fas ligand system probably plays a critical role in the development of renal tubular epithelial cell injury through apoptotic cell death.


* 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: nao777nk{at}amugw.aichi-med-u.ac.jp.


Infection and Immunity, August 1999, p. 4112-4118, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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