There is growing evidence for an interplay between inflammatory and coagulation pathways in acute and chronic inflammatory diseases. However, it remains unclear whether components of the coagulation pathway, such as tissue factor (TF), contribute to intestinal inflammation, and whether targeting TF will blunt the inflammatory cell recruitment, tissue injury, and enhanced thrombus formation that occur in experimental colitis. Mice were fed 3% dextran sodium sulfate (DSS) to induce colonic inflammation, with some mice receiving a mouse TF-blocking antibody (muTF-Ab). The adhesion of leukocytes and platelets in colonic venules, light/dye-induced thrombus formation in cremaster muscle microvessels, as well as disease activity index, thrombin–antithrombin (TAT) complexes in plasma, and histopathologic changes in the colonic mucosa were monitored in untreated and muTF-Ab–treated colitic mice. In untreated mice, DSS elicited the recruitment of adherent leukocytes and platelets in colonic venules, caused gross and histologic injury, increased plasma TAT complexes, and enhanced thrombus formation in muscle arterioles. muTF-Ab prevented elevation in TAT complexes, reduced blood cell recruitment and tissue injury, and blunted thrombus formation in DSS colitic mice. These findings implicate TF in intestinal inflammation and support an interaction between inflammation and coagulation in experimental colitis.
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9 July 2007
Article|
June 11 2007
Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis
Christoph Anthoni,
Christoph Anthoni
1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130
2Department of General Surgery, Westphalian Wilhelms-University, 48149 Münster, Germany
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Janice Russell,
Janice Russell
1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130
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Katherine C. Wood,
Katherine C. Wood
1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130
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Karen Y. Stokes,
Karen Y. Stokes
1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130
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Thorsten Vowinkel,
Thorsten Vowinkel
2Department of General Surgery, Westphalian Wilhelms-University, 48149 Münster, Germany
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Daniel Kirchhofer,
Daniel Kirchhofer
3Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080
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D. Neil Granger
D. Neil Granger
1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130
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Christoph Anthoni
1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130
2Department of General Surgery, Westphalian Wilhelms-University, 48149 Münster, Germany
Janice Russell
1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130
Katherine C. Wood
1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130
Karen Y. Stokes
1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130
Thorsten Vowinkel
2Department of General Surgery, Westphalian Wilhelms-University, 48149 Münster, Germany
Daniel Kirchhofer
3Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080
D. Neil Granger
1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130
CORRESPONDENCE D. Neil Granger: [email protected]
Abbreviations used: Ab, antibody; DAI, disease activity index; DSS, dextran sodium sulfate; IBD, inflammatory bowel disease; muTF-Ab, mouse TF-blocking Ab; PAR, protease-activated receptor; TAT, thrombin–antithrombin; TF, tissue factor.
Received:
November 08 2006
Accepted:
May 23 2007
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (7): 1595–1601.
Article history
Received:
November 08 2006
Accepted:
May 23 2007
Citation
Christoph Anthoni, Janice Russell, Katherine C. Wood, Karen Y. Stokes, Thorsten Vowinkel, Daniel Kirchhofer, D. Neil Granger; Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis . J Exp Med 9 July 2007; 204 (7): 1595–1601. doi: https://doi.org/10.1084/jem.20062354
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