ative hepatic failure in such cases is still poorly understood, The aim of this study was to assess the hypothesis that we have previously noticed appreciable accumulations of hepatic failure after extensive hepatectomy in patients polymorphonuclear neutrophils (PMNs) in the liver at auwith obstructive jaundice (OJ) may be mediated by polytopsy. 3 Aside from the cardinal role of PMNs in the host morphonuclear neutrophils (PMN). In the OJ group, rats defense, it has been shown that activated PMNs are impliunderwent a partial hepatectomy of 78% after 2 weeks cated in several serious disorders, such as adult respiratory of cholestasis and subsequent external biliary drainage distress syndrome, rheumatoid arthritis, myocardial reperfufor 5 days. In the sham-operated control group, rats were sion injury, inflammatory bowel disease, 4,5 and idiopathic partially hepatectomized 19 days after the sham surgery.
pulmonary fibrosis. 6 These conditions are characterized his-The concentration of the serum cytokine-induced neutologically by the remarkable accumulation of PMNs at the trophil chemoattractant (CINC), which is homologous injured tissue site. Additionally in liver diseases, infiltration with the growth-related oncogene (gro) product, a memof PMNs can be seen in alcoholic hepatitis 7,8 and reperfusion ber of the human interleukin (IL)-8 family, and a major injury. 9 Recently, the importance of vascular endothelial cell neutrophil chemotactic factor in rats, increased concominjury has been established in these types of organ damage. itantly with accumulation of PMNs in the hepatic sinu-Some investigators have reported that the injury of sinusoisoids during cholestasis and subsequent external draindal endothelial cells (SECs) plays an important role in the age. However, changes in the serum purine nucleoside development of hepatic damage. [10][11][12] It is well known that phosphorylase (PNP)/alanine transaminase (ALT) ratio
PMNs have the capacity to injure vascular endothelial cells as a marker of sinusoidal endothelial cell (SEC) injury and are one of the most important effector cells for endotheshowed no significant differences between the two lial injury. [13][14][15][16] These findings suggest that PMNs may medigroups. Intercellular adhesion molecule-1 (ICAM-1) exate SEC injury with severe hepatic damage after extensive pression on SECs was not affected by cholestasis and hepatectomy in patients with OJ as well. external drainage. After partial hepatectomy, the serum
The process of PMN-mediated endothelial cell injury in-CINC concentration immediately elevated more promicludes accumulation of PMNs at the target site and their nently in the OJ group than in the sham-operated conpriming and activation. Several chemotactic and activating trol group, and accumulation of PMNs in the sinusoids factors are reported to modulate the process, including anawas more obvious and prolonged in the former. ICAM-1 phylatoxin C5a, 17 N-formyl-methionyl peptides, 18 leukotriene expression was enhanced in both groups with a peak B 4 , 19 platelet-activating factor, 20 and interleukin (IL)-8. 5,21 In between 24 and 48 hours after partial hepatectomy. At humans, IL-8 is the major mediator for the chemotaxis of this peak period, a significantly higher PNP/ALT ratio PMNs and is involved in several pathophysiological condiwas observed in the OJ group. These results suggest that tions. 5,21 In rats, however, the counterpart of IL-8 has not accumulation of PMNs in the sinusoidal space and yet been identified. IL-8 has considerable sequence homology ICAM-1 expression on SECs might be closely associated with various peptides such as growth-related oncogene (gro) with the development of SEC injury after extensive hepproduct, platelet basic protein, platelet factor 4, and interatectomy in cholestasis. (HEPATOLOGY 1997;25:636-641.) feron gamma-inducible protein-10. 5 Cytokine-induced neutrophil chemoattractant (CINC), which has gro homology, is reported to be a major neutrophil chemotactic factor in rats Obstructive jaundice (OJ) is a risk factor for high surgical morbidity and mortality rates, particularly in major surgery. 1 and a likely functional equivalent of IL-8 in humans. 22,23 For the induction and maintenance of PMN cytotoxicity, Extensive hepatectomy is often used for the treatment of hepatobiliary carcinoma invading the hepatic hilus, which is PMN adhesion to target cells is a prerequisite. 24,25 The adhesion molecules, CD11a/CD18 and CD11b/CD18, members of usually associated with OJ. Hepatic failure after extensive hepatectomy, however, is occasionally experienced in those the integrin family expressed on the surface of activated PMNs, have been shown to promote PMN adherence to the patients with OJ, even after effective relief of cholestasis by preoperative drainage. 2 Although the mechanism of postoper-vascular endothelium in vitro. 26 These molecules bind to their ligand, intercellular adhesion molecule-1 (ICAM-1), on the surface of endothelial cells. 27 Therefore, ICAM-1 can be considered to be a key molecule of PMN-SEC interaction.