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Role of the coagulation system in experimental colitis
Author(s) -
Anthoni Christoph,
Vowinkel Thorsten,
Senninger Norbert,
Kirchhofer Daniel,
Granger D Neil
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a704
Subject(s) - colitis , inflammatory bowel disease , intravital microscopy , tissue factor , coagulation , medicine , platelet , immunology , inflammation , pathology , microcirculation , disease
Growing evidence indicates that there is significant “cross‐talk” between inflammatory and coagulation pathways. While patients with inflammatory bowel disease exhibit an increased incidence of thrombosis, it remains unclear whether the coagulation cascade contributes to the intestinal inflammation. The objective of this study was to determine whether tissue factor (TF) contributes to leukocyte/platelet‐endothelial adhesion, tissue injury, and disease severity in experimental murine colitis induced by feeding C57Bl/6 mice 3% dextran sodium sulfate (DSS) in drinking water for 6 days. Some mice were treated with a monoclonal antibody (mAb) against murine tissue factor (muTF‐mAb) two times (20mg/kg, ip) during the 6 days of DSS ingestion. Colitis was assessed by a disease activity index (DAI) and histology. Intravital fluorescence microscopy was used to quantify leukocyte and platelet adhesion in venules. In untreated mice, DSS resulted in an increased DAI, colon shortening, an increased colon weight/length ratio, and a profound increase in the number of adherent leukocytes and platelets in colonic venules. All of these responses to DSS were significantly attenuated in DSS mice treated with muTF‐mAb. These findings support a link between the coagulation and inflammatory pathways in experimental colitis and implicate tissue factor as a major pro‐inflammatory agent in this model. (Supported by DK65649)