Hepatic inflammation following 70% hepatectomy may be related to up-regulation of epithelial neutrophil activating protein-78.
Tumor necrosis factor-alpha (TNF) is known to be released after partial hepatectomy. Furthermore, TNF triggers the release of chemotactic cytokines, such as epithelial neutrophil activating protein (ENA-78), which are important for neutrophil chemotaxis, activation, and propagation of the inflammatory response. We now postulate that ENA-78 may play a role the hepatic inflammatory response that occurs following partial hepatectomy. Rats were subjected to 70% hepatectomy or sham laparotomy and were killed in a time-dependent manner. Hepatic neutrophil influx, as assessed by myeloperoxidase (MPO) levels, serum alanine aminotransferase (ALT), and hepatic TNF and ENA-78 levels, as measured by ELISA, were evaluated at 1, 6, and 12 h following operation. MPO levels became significantly elevated within 6 h of hepatectomy and remained elevated at 12 h. Serum ALT became significantly elevated within 1 h of hepatectomy and continued to rise at 12 h. Hepatic TNF and ENA-78 were also increased significantly after hepatectomy. Next, rats undergoing 70% hepatectomy were treated with neutralizing anti-ENA-78 serum; this resulted in a significant decrease in hepatic MPO and serum ALT, suggesting less hepatic injury. To determine whether ENA-78 release was induced by TNF is this model, rats were treated with neutralizing anti-TNF serum and hepatic ENA-78 levels measured 6 h posthepatectomy. ENA-78 levels were significantly decreased in the animals receiving the anti-TNF serum, suggesting that ENA-78 is released in response to TNF in this model. These data suggest that TNF triggers the release of ENA-78 following 70% hepatectomy and that ENA-78 contributes to the hepatic neutrophil influx and liver injury following 70% hepatectomy.
Colletti
L M
LM
Department of Surgery, University of Michigan, Ann Arbor 48109-0331, USA.
Kunkel
S L
SL
Green
M
M
Burdick
M
M
Strieter
R M
RM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D004195:Disease Models, Animal; D006498:Hepatectomy / Q000379:methods*; D006520:Hepatitis, Animal / Q000378:metabolism*; D007106:Immune Sera / Q000494:pharmacology; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011300:Preoperative Care; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D007106:Immune Sera; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D000410:Alanine Transaminase