Activated Kupffer cells cause a hypermetabolic state after gentle in situ manipulation of liver in rats

Harvesting trauma to the graft dramatically decreases survival after liver transplantation. Since activated Kupffer cells play a role in primary nonfunction, the purpose of this study was to test the hypothesis that organ manipulation activates Kupffer cells. To mimic what occurs with donor hepatect...

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Published in:American journal of physiology: Gastrointestinal and liver physiology 2001-06, Vol.280 (6), p.G1076-G1082
Main Authors: Schemmer, P, Enomoto, N, Bradford, B U, Bunzendahl, H, Raleigh, J A, Lemasters, J J, Thurman, R G
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Dinoprostone - biosynthesis
Female
Glycogen - deficiency
Hypoxia - etiology
Kupffer Cells - physiology
Liver - metabolism
Liver Diseases - etiology
Physical Stimulation
Rats
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha - biosynthesis
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Summary:Harvesting trauma to the graft dramatically decreases survival after liver transplantation. Since activated Kupffer cells play a role in primary nonfunction, the purpose of this study was to test the hypothesis that organ manipulation activates Kupffer cells. To mimic what occurs with donor hepatectomy, livers from Sprague-Dawley rats underwent dissection with or without gentle organ manipulation in a standardized manner in situ. Perfused livers exhibited normal values for O(2) uptake (105 +/- 5 micromol. g(-1). h(-1)) measured polarigraphically; however, 2 h after organ manipulation, values increased significantly to 160 +/- 8 micromol. g(-1). h(-1) and binding of pimonidazole, a hypoxia marker, increased about threefold (P < 0.05). Moreover, Kupffer cells from manipulated livers produced three- to fourfold more tumor necrosis factor-alpha and PGE(2), whereas intracellular calcium concentration increased twofold after lipopolysaccharide compared with unmanipulated controls (P < 0.05). Gadolinium chloride and glycine prevented both activation of Kupffer cells and effects of organ manipulation. Furthermore, indomethacin given 1 h before manipulation prevented the hypermetabolic state, hypoxia, depletion of glycogen, and release of PGE(2) from Kupffer cells. These data indicate that gentle organ manipulation during surgery activates Kupffer cells, leading to metabolic changes dependent on PGE(2) from Kupffer cells, which most likely impairs liver function. Thus modulation of Kupffer cell function before organ harvest could be beneficial in human liver transplantation and surgery.
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.2001.280.6.G1076