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Infection and Immunity, May 1999, p. 2540-2546, Vol. 67, No. 5
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Lipopolysaccharide Induction of Tissue Factor Expression in Rabbits

Jonathan Erlich,1 Colleen Fearns,2 John Mathison,2 Richard J. Ulevitch,2 and Nigel Mackman1,*

Departments of Immunology and Vascular Biology1 and Department of Immunology,2 The Scripps Research Institute, La Jolla, California

Received 28 August 1998/Returned for modification 15 October 1998/Accepted 21 January 1999

Tissue factor (TF) is the major activator of the coagulation protease cascade and contributes to lethality in sepsis. Despite several studies analyzing TF expression in animal models of endotoxemia, there remains debate about the cell types that are induced to express TF in different tissues. In this study, we performed a detailed analysis of the induction of TF mRNA and protein expression in two rabbit models of endotoxemia to better understand the cell types that may contribute to local fibrin deposition and disseminated intravascular coagulation. Northern blot analysis demonstrated that lipopolysaccharide (LPS) increased TF expression in the brain, lung, and kidney. In situ hybridization showed that TF mRNA expression was increased in cells identified morphologically as epithelial cells in the lung and as astrocytes in the brain. In the kidney, in situ hybridization experiments and immunohistochemical analysis showed that TF mRNA and protein expression was increased in renal glomeruli and induced in tubular epithelium. Dual staining for TF and vWF failed to demonstrate TF expression in endothelial cells in LPS-treated animals. These results demonstrate that TF expression is induced in many different cell types in LPS-treated rabbits, which may contribute to local fibrin deposition and tissue injury during endotoxemia.

* Corresponding author. Mailing address: The Scripps Research Institute, IMM-17, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (619) 784-8594. Fax: (619) 784-8480. E-mail: nmackman{at}scripps.edu.

Infection and Immunity, May 1999, p. 2540-2546, Vol. 67, No. 5
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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