Obstructive jaundice impedes hepatic microcirculation in mice.
OBJECTIVE
To explore the mechanisms by which postoperative complications frequently occur in patients with obstructive jaundice, we examined the effects of obstructive jaundice on hepatic microcirculation and Kupffer cell activity in mice.


METHODS
Common bile duct ligation and division was performed on C57BL/6 mice to induce obstructive jaundice. One and 2 weeks after surgery, sinusoidal perfusion, leukocyte rolling and sticking in the postsinusoidal venules, and diameters of sinusoids containing blood flow were evaluated using intravital microscopy. Kupffer cell phagocytic activity was estimated by the ratio of Kupffer cells that phagocytosed fluorescent-labeled particles to sinusoids containing blood flow.


RESULTS
The sinusoidal perfusion significantly decreased in the jaundiced mice associated with a significant increase in the number of rolling leukocytes and sticking leukocytes. Obstructive jaundice significantly reduced diameters of sinusoids due to Kupffer cell swelling. Kupffer cell phagocytic activity significantly increased in the jaundiced mice associated with enhanced expression of tumor necrosis factor-alpha mRNA in the liver. These data suggest that obstructive jaundice stimulates Kupffer cell to induce inflammatory mediators and leukocyte-endothelial cell interaction.


CONCLUSIONS
Leukocyte adhesion and narrowing of sinusoids due to Kupffer cell activation might impede hepatic microcirculation resulting in hypoxic damage of the liver with obstructive jaundice.
Okaya
Tomohisa
T
Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Nakagawa
Koji
K
Kimura
Fumio
F
Shimizu
Hiroaki
H
Yoshidome
Hiroyuki
H
Ohtsuka
Masayuki
M
Morita
Yasuhiro
Y
Miyazaki
Masaru
M
D000818:Animals; D041781:Jaundice, Obstructive / Q000503:physiopathology*; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction