Fasudil, a Rho-kinase inhibitor, inhibits leukocyte adhesion in inflamed large blood vessels in vivo.
OBJECTIVE
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.


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.
Slotta
J E
JE
Department of Surgery, Malmö University Hospital, Lund University, 20502 Malmö, Sweden.
Braun
O O
OO
Menger
M D
MD
Thorlacius
H
H
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001167:Arteritis / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects*; D005263:Femoral Artery / Q000276:immunology; D005268:Femoral Vein / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D036904:Leukocyte Rolling / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects* / Q000201:enzymology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010689:Phlebitis / Q000276:immunology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C049347:fasudil