Amelioration of sinusoidal endothelial cell damage by Kupffer cell blockade during cold preservation of rat liver.
Recent studies have shown that Kupffer cell function is enhanced in the cold-preserved liver, and blockade of Kupffer cells attenuates the injury induced by cold preservation with subsequent reperfusion. This study was designed to investigate the contribution of Kupffer cell blockade with gadolinium chloride (GdCl3) to the rescue of sinusoidal endothelial cell (SEC) damage by comparing the time-related morphological and ultrastructural changes. GdCl3 injection reduced the number of Kupffer cells reactive with monoclonal antibodies ED2 and Ki-M2R directed against macrophage. Scanning electron microscopy revealed the prominent string-like appearance of the SEC processes at 24 hr of preservation in the control; the SECs were better preserved in the GdCl3-pretreated group. Transmission electron microscopy showed detachment of the sinusoidal epithelia at 12 hr of preservation in the control; it was not seen in the GdCl3-pretreated group. At 24 hr of preservation, the SECs were better preserved in the GdCl3-pretreated group. Microvascular casts from the control group showed a disturbance in the radial arrangement of the sinusoids, significant dilation of the sinusoidal caliber at 24 hr, and discontinuity of the sinusoids with extravasation of the casting material at 36 hr of preservation. These changes were also minimized in the GdCl3-pretreated group. In conclusion, the present study demonstrates that Kupffer cells are strongly involved in the morphological integrity of SECs and that blockade of the activation of Kupffer cells would be effective for the prevention of damage to SECs and maintenance of the sinusoidal architecture during cold preservation of the liver tissure.
Niwano
M
M
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Arii
S
S
Monden
K
K
Ishiguro
S
S
Nakamura
T
T
Mizumoto
M
M
Takeda
Y
Y
Fujioka
M
M
Imamura
M
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D016319:Corrosion Casting; D015925:Cryopreservation; D004727:Endothelium / Q000166:cytology; D005682:Gadolinium / Q000494:pharmacology; D007728:Kupffer Cells / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000098:blood supply / Q000166:cytology* / Q000648:ultrastructure; D008297:Male; D008833:Microcirculation; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D005682:Gadolinium; C038958:gadolinium chloride