Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis.
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.
Anthoni
Christoph
C
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
Russell
Janice
J
Wood
Katherine C
KC
Stokes
Karen Y
KY
Vowinkel
Thorsten
T
Kirchhofer
Daniel
D
Granger
D Neil
DN
D000818:Animals; D000991:Antithrombins / Q000502:physiology; D001777:Blood Coagulation / Q000502:physiology; D001792:Blood Platelets / Q000502:physiology; D003092:Colitis / Q000473:pathology* / Q000503:physiopathology*; D003106:Colon / Q000098:blood supply; D004195:Disease Models, Animal; D007249:Inflammation / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology; D051379:Mice; D008833:Microcirculation / Q000502:physiology; D013925:Thromboplastin / Q000502:physiology*; D013927:Thrombosis / Q000503:physiopathology*
D000991:Antithrombins; D013925:Thromboplastin