Lymph vessel expansion and function in the development of hepatic fibrosis and cirrhosis.
The process of lymph vessel expansion and function in the development of CCl4-induced hepatic fibrosis and cirrhosis was studied using intravital fluorescence microscopy of the rat liver. The unique aspect of our approach was the use of high molecular fluorescein-isothiocyanate-labeled dextran (MW, 150,000) as fluorescent marker, which allowed for simultaneous assessment of both 1) the macromolecular blood hepatocytic exchange from the sinusoidal microvasculature (extra-/intrasinusoidal gray level intensity at 1, 3, 5, and 10 minutes after intravenous injection) and 2) the hepatic lymph system. In animals exposed with CCl4 up to 4 weeks, macromolecular trans-sinusoidal exchange was found progressively delayed. This was strongly associated with lymph vessel expansion and function, as indicated by a continuous increase of lymph vessel density and area. Delay of macromolecular exchange and lymph vessel expansion was found not further enhanced at fibrotic and cirrhotic stages of 8- and 12-week CCl4-exposed livers. Linear regression analysis revealed a strong negative correlation between lymphatic network density development and macromolecular trans-sinusoidal exchange (r2 = 0.99; P < 0.01). Thus, our study provides for the first time direct evidence for the pivotal role of lymphatic function for macromolecular transport in case of deteriorated sinusoidal hepatocellular exchange capacity.
Vollmar
B
B
Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
Wolf
B
B
Siegmund
S
S
Katsen
A D
AD
Menger
M D
MD
D000818:Animals; D002251:Carbon Tetrachloride; D005355:Fibrosis; D007700:Kinetics; D008099:Liver / Q000098:blood supply; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D008208:Lymphatic System / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000473:pathology / Q000503:physiopathology; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D051381:Rats; D017207:Rats, Sprague-Dawley
D002251:Carbon Tetrachloride