OBJECTIVE AND DESIGN: Emerging data suggest that Rho-kinase signaling may regulate numerous aspects of inflammatory reactions. Herein, we investigated the role of Rho-kinase in inflammatory interactions between leukocytes and the endothelium in femoral arteries and veins in vivo. MATERIAL AND METHODS: Mice were injected with lipopolysaccharide (LPS) and Rho-kinase was inhibited by pre-treatment with fasudil, which is a highly selective inhibitor of Rho-kinase. Six hours after LPS challenge, intravital fluorescence microscopy of the femoral vessels was performed and leukocyte-endothelium interactions were visualized after in vivo staining with rhodamine 6G. RESULTS: LPS increased leukocyte rolling and adhesion in femoral arteries and veins. Pre-treatment with fasudil had no effect on leukocyte rolling but significantly decreased venular leukocyte adhesion by 85% and completely abrogated leukocyte adhesion in femoral arteries in endotoxin-treated mice. CONCLUSIONS: We conclude that Rho-kinase signaling regulates LPS-induced leukocyte adhesion in femoral arteries and veins in vivo and that inhibition of Rho-kinase may be useful in the treatment of pathological inflammation in large blood vessels of the vascular system.
OBJECTIVE AND DESIGN: Emerging data suggest that Rho-kinase signaling may regulate numerous aspects of inflammatory reactions. Herein, we investigated the role of Rho-kinase in inflammatory interactions between leukocytes and the endothelium in femoral arteries and veins in vivo. MATERIAL AND METHODS:Mice were injected with lipopolysaccharide (LPS) and Rho-kinase was inhibited by pre-treatment with fasudil, which is a highly selective inhibitor of Rho-kinase. Six hours after LPS challenge, intravital fluorescence microscopy of the femoral vessels was performed and leukocyte-endothelium interactions were visualized after in vivo staining with rhodamine 6G. RESULTS:LPS increased leukocyte rolling and adhesion in femoral arteries and veins. Pre-treatment with fasudil had no effect on leukocyte rolling but significantly decreased venular leukocyte adhesion by 85% and completely abrogated leukocyte adhesion in femoral arteries in endotoxin-treated mice. CONCLUSIONS: We conclude that Rho-kinase signaling regulates LPS-induced leukocyte adhesion in femoral arteries and veins in vivo and that inhibition of Rho-kinase may be useful in the treatment of pathological inflammation in large blood vessels of the vascular system.
Authors: Stefan Santen; Yusheng Wang; Matthias W Laschke; Michael D Menger; Bengt Jeppsson; Henrik Thorlacius Journal: Int J Colorectal Dis Date: 2010-07-01 Impact factor: 2.571