Sinusoidal endothelial cell damage by activated macrophages in rat liver necrosis

Arai, Masahiro; Mochida, Satoshi; Ohno, Akihiko; Ogata, Itsuro; Fujiwara, Kenji

doi:10.1016/0016-5085(93)90357-i

Cited by 87 publications

(47 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5 The extent of sinusoidal cell injury can be evaluated by measuring both PNP and ALT activities in the serum and liver perfusates, 5,27 because the ratio of ALT activity to PNP activity is about 5:1 in isolated hepatocytes. 5 Serum activities of PNP and ALT increased before endotoxin administration in 70% hepatectomized rats (Experiment I). These increases may result from leakage of both enzymes from necrotic liver tissue remaining after partial liver resection, because no necrotic areas were observed in remnant liver on light microscopy.…”

Section: Discussionmentioning

confidence: 99%

“…5 Cells were cultured in DMEM with 10% heat-inactivated FCS under 95% air and 5% CO 2 at 37°C on 35-mm culture dishes (Falcon 3001; Becton Dickinson Labware, Lincoln Park, NJ) at a density of 2 ϫ 10 6 cells per milliliter per dish. After 1-hour incubation, nonadherent cells were removed by washing with phosphate-buffered saline (PBS).…”

Section: Isolation Of Kupffer Cellsmentioning

confidence: 99%

“…7 In the P. acnes model, activated hepatic macrophages after endotoxin stimulation destroyed sinusoidal endothelial cells by releasing superoxide anions and tumor necrosis factor ␣ and provoked fibrin deposition in the hepatic sinusoids. 2,5,6,[8][9][10] Such mechanisms, however, may not be involved in the development of sinusoidal fibrin deposition in the partialhepatectomy model, because polyclonal antibody against tumor necrosis factor ␣ and superoxide anion dismutase were ineffective for attenuation of the liver injury. 3,6 Moreover, selective eradication of large hepatic macrophages responsible for production of cytotoxic mediators using gadolinium chloride 11 significantly attenuated liver injury in the P. acnes model, but not liver injury in the partial-hepatectomy model, 5,6 whereas suppression of activation of Kupffer cells and hepatic macrophages by pretreatment of gum arabic 12 produced similar attenuation of liver injuries in both models.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Deranged blood coagulation equilibrium as a factor of massive liver necrosis following endotoxin administration in partially hepatectomized rats

et al. 1999

Self Cite

View full text Add to dashboard Cite

Activated Kupffer cells provoke massive liver necrosis after endotoxin stimulation through microcirculatory disturbance caused by sinusoidal fibrin deposition in rats undergoing 70% hepatectomy. In these rats, serum activities of purine nucleoside phosphorylase (PNP) and alanine transaminase (ALT) were increased at 1 and 5 hours, respectively, following endotoxin administration. When 70% resected liver was perfused with Dulbecco's modified Eagle medium (DMEM) containing heat-inactivated fetal calf serum, the increase in both enzyme activities was not affected by addition of endotoxin during perfusion, suggesting that activated Kupffer cells injured neither sinusoidal endothelial cells nor hepatocytes. The activity of tissue factor, an initiator of blood coagulation cascade, was much higher in Kupffer cells isolated from partially hepatectomized rats than in those from normal rats. In contrast, mRNA expressions of tissue factor pathway inhibitor (TFPI) as well as thrombomodulin were almost undetectable in normal and partially resected livers. When recombinant human TFPI was injected intravenously in 70% hepatectomized rats, TFPI was markedly stained on the surfaces of sinusoidal endothelial cells and microvilli of hepatocytes on immunohistochemistry. In these rats, endotoxin-induced liver injury was significantly attenuated compared with rats given no TFPI. Similar attenuation was also found in rats receiving recombinant human thrombomodulin. These results suggest that fibrin deposition developing in 70% hepatectomized rats after endotoxin administration may be caused by deranged blood coagulation in the hepatic sinusoids through increasing tissue factor activity in Massive liver necrosis develops after endotoxin administration in rats pretreated with heat-killed Propionibacterium acnes or those undergoing 70% liver resection as a result of microcirculatory disturbance caused by sinusoidal fibrin deposition. [1][2][3] In both models, Kupffer cells and hepatic macrophages are activated to provoke endothelial cell injury and fibrin deposition in the hepatic sinusoids. 2-6 However, an apparent difference exists in the stimulatory state of Kupffer cells and hepatic macrophages between both models, because activated Kupffer cells in the partial-hepatectomy model produced fewer cytotoxic mediators such as superoxide anions and tumor necrosis factor ␣ in response to endotoxin administration compared with activated hepatic macrophages in the P. acnes model, 6,7 although both cells can release a large amount of superoxide anions after stimulation with phorbol 12-myristate 13-acetate. 3,4 Northern blot analysis revealed that such difference resulted from expression of endotoxin receptors on the cells; P. acnes-treated rat liver showed increased mRNA expression of CD14, a receptor for lipopolysaccharide and its binding protein complex, compared with normal liver, while such expression was markedly reduced in partially hepatectomized rat liver. 7 In the P. acnes model, activated hepatic macrophages after endotoxin stimulatio...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Isolation Of Kupffer Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Deranged blood coagulation equilibrium as a factor of massive liver necrosis following endotoxin administration in partially hepatectomized rats

et al. 1999

Self Cite

View full text Add to dashboard Cite

show abstract

“…Chemokine network through osteopontin, an extracellular matrix which can also promote migration of macrophages, was associated with macrophage infiltration into the liver in this model (13,14). These macrophages are activated to produce a large amountof TNF-aand superoxide anions (15,16) and produce destruction of endothelial cells leading to development of fibrin deposition in the hepatic sinusoids (16,17). In contrast, Kupffer cells became activated through bacterial translocation following 70% liver resection in rats (18,19).…”

Section: Local Factors In the Livermentioning

confidence: 88%

“…These Kupffer cells are rich in the activity of tissue factor, an initiator of blood coagulation cascade, and fibrin deposition develops after LPSadministration in partially hepatectomized rats as a result of deranged blood coagulation equilibrium in the hepatic sinusoids (20). It is noteworthy that hepatocyte damage occurs in both models due to microcirculatory disturbance induced by sinusoidal fibrin deposition (16,20).…”

Section: Local Factors In the Livermentioning

confidence: 99%