Hepatocyte injury during post-operative sepsis: activated neutrophils as potential mediators.
We evaluated the concept that the vascular entrance of both bacterial and nonbacterial particulate material could lead to hepatic parenchymal cell injury, either due to postphagocytic Kupffer cell activity or the margination of activated leukocytes in the liver. Injection of denatured, collagen-coated particles as well as heat-killed bacteria were used as particulate challenges. Hepatic parenchymal cell injury in vivo during postoperative sepsis was evaluated by plasma aspartate aminotransferase (AST) and ornithine carbamyl transferase (OCT) enzyme levels over 3-72 h. AST and OCT levels elevated following either laparotomy plus cecal ligation (mild sepsis) or laparotomy plus cecal ligation with puncture (severe sepsis), with the peak level at 24 h. In addition, the direct intravenous injection of either nonbacterial foreign particles or heat-killed Pseudomonas aeruginosa into normal rats also produced a dose-dependent elevation of AST and OCT. The plasma level of either AST or OCT actually increased 350-400% after injection of the non-bacterial particles. A similar dose related elevation in enzymes followed the intravenous injection of heat-killed Pseudomonas. To differentiate the potential contribution of activated hepatic Kupffer cells versus activated marginated neutrophils to the in vivo hepatic injury, we determined the release of the hepatic specific enzyme OCT by cultured hepatic parenchymal cells when they were exposed to isolated Kupffer cells or isolated PMNs that were activated by exposure to dead bacteria. Bacteria alone when added to cultured hepatocytes did not induce significant OCT release. In contrast, activated PMNs but not Kupffer cells induced a significant (p less than 0.05) release of OCT from parenchymal cells into the culture media. Thus, in vivo transient hepatic parenchymal cell injury with post-operative sepsis may be mediated by the margination of activated PMNs in the liver.
Department of Physiology, Albany Medical College, Union University, New York 12208.
J M
JM
Holman
T M
TM
Saba
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D007728:Kupffer Cells / Q000502:physiology; D008099:Liver / Q000473:pathology*; D008107:Liver Diseases / Q000209:etiology; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D009954:Ornithine Carbamoyltransferase / Q000097:blood; D010587:Phagocytosis; D011183:Postoperative Complications / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D018805:Sepsis / Q000473:pathology*
D009954:Ornithine Carbamoyltransferase; D001219:Aspartate Aminotransferases