Perforin and granzyme B lytic protein expression during chronic viral and autoimmune hepatitis

Tordjmann, Thierry; Soulié, Annie; Guettier, Catherine; Schmidt, Michel; Berthou, Christian; Beaugrand, Michel; Sasportes, M

doi:10.1111/j.1600-0676.1998.tb00823.x

Cited by 53 publications

(23 citation statements)

References 35 publications

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“…In an effort to understand the etiology and treatment of liver ischemia-reperfusion injury, many studies have been performed in light of apoptosis [12,31,32] because apoptosis is an active cell death controlled by a discrete set of genes, and altering the expression of those genes or mimicking its transduction pathway could allow manipulation of its induction. In the present study, we show that the structural and functional liver injury accompanying hepatocyte apoptosis is induced by the ischemia-reperfusion protocol, and this apoptosis can be mediated through the Fas/FasL system.…”

Section: Discussionmentioning

confidence: 99%

“…A single injection of agonistic anti-Fas antibody leads to massive apoptotic cell death of hepatocytes, resulting in fulminant hepatitis [30,31], and perforin and granzymes have been shown to be involved in liver injury due to viral hepatitis [32][33][34]. A crucial role for alveolar macrophages in the inflammatory response associated with lung injury has been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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Blockade of the Fas/Fas ligand interaction suppresses hepatocyte apoptosis in ischemia-reperfusion rat liver

et al. 2008

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Hepatic ischemia-reperfusion injury remains a significant problem for liver surgery, including transplantation, and apoptosis has been implicated in this type of hepatic injury. Here we found that through the Fas/Fas ligand interaction apoptosis is involved in the late phase of hepatic ischemia-reperfusion injury. The appearance of apoptotic hepatocytes increases significantly after reperfusion, reaching a maximum 12 h after reperfusion. The transcription levels of Fas and Fas ligand are increased after reperfusion. Fas is expressed on hepatocytes, while Fas ligand is expressed on infiltrating immune cells. A close spatial and temporal association of Fas expression and apoptotic cells is demonstrated in the histological observation. These results suggest that infiltrating cells induce apoptosis of hepatocytes through the Fas/Fas ligand interaction, leading to hepatocyte injury. Furthermore, an injection of anti-Fas antibody or neutralizing anti-Fas ligand antibody results in a dramatic decrease in the occurrence of hepatocyte apoptosis and hepatic infiltration of macrophages and natural killer cells as well as liver injury. Our results suggest that blockage of the Fas/Fas ligand interaction is a promising strategy for suppression of hepatic ischemia-reperfusion injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Blockade of the Fas/Fas ligand interaction suppresses hepatocyte apoptosis in ischemia-reperfusion rat liver

et al. 2008

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“…Alternatively, while restoring perforin may be sufficient to maintain fungal killing, additional cytolytic molecules may have to be restored to maintain tumor killing. Perforin colocalizes with other cytolytic molecules in their lytic granules, including granzymes (26,48,56). Besides inducing lysis of target cells directly, perforin also aids entry of granzymes into the cell, resulting in apoptosis (5,11,24,25,38).…”

Section: Discussionmentioning

confidence: 99%

Cryptococcus neoformansDirectly Stimulates Perforin Production and Rearms NK Cells for Enhanced Anticryptococcal Microbicidal Activity

Marr¹,

Jones²,

Zheng

et al. 2009

Infect Immun

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NK cells, in addition to possessing antitumor and antiviral activity, exhibit perforin-dependent microbicidal activity against the opportunistic pathogen Cryptococcus neoformans. However, the factors controlling this response, particularly whether the pathogen itself provides an activation or rearming signal, are largely unknown. The current studies were performed to determine whether exposure to this fungus alters subsequent NK cell anticryptococcal activity. NK cells lost perforin and mobilized lysosome-associated membrane protein 1 to the cell surface following incubation with the fungus, indicating that degranulation had occurred. Despite a reduced perforin content during killing, NK cells acquired an enhanced ability to kill C. neoformans, as demonstrated using auxotrophs that allowed independent assessment of the killing of two strains. De novo protein synthesis was required for optimal killing; however, there was no evidence that a soluble factor contributed to the enhanced anticryptococcal activity. Exposure of NK cells to C. neoformans caused the cells to rearm, as demonstrated by increased perforin mRNA levels and enhanced loss of perforin when transcription was blocked. Degranulation alone was insufficient to provide the activation signal as NK cells lost anticryptococcal activity following treatment with strontium chloride. However, NK cells regained the activity upon prolonged exposure to C. neoformans, which is consistent with activation by the microbe. The enhanced cytotoxicity did not extend to tumor killing since NK cells exposed to C. neoformans failed to kill NK-sensitive tumor targets (K562 cells). These studies demonstrate that there is contact-mediated microbe-specific rearming and activation of microbicidal activity that are necessary for optimal killing of C. neoformans.

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“…Increased numbers of Kupffer cells have been found in regions of liver fibrosis in the setting of chronic viral hepatitis [60] . Viral hepatitis has also been shown to induce Kupffer cells to release cytotoxic molecules that kill not only infected hepatocytes but also non-infected cells [61,62] . It is likely that Kupffer cells are involved in the pathogenesis of many types of liver pathologies and it may be the case that their activation is multifactorial in patients with AH as well as other hepatic comorbidities.…”

Section: Importance Of Kupffer Cells In Alcoholic Hepatitismentioning

confidence: 99%

Alcoholic hepatitis: The pivotal role of Kupffer cells

Suraweera

Weeratunga

et al. 2015

WJGP

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Kupffer cells play a central role in the pathogenesis of alcoholic hepatitis (AH). It is believed that alcohol increases the gut permeability that results in raised levels of serum endotoxins containing lipopolysaccharides (LPS). LPS binds to LPS-binding proteins and presents it to a membrane glycoprotein called CD14, which then activates Kupffer cells via a receptor called tolllike receptor 4. This endotoxin mediated activation of Kupffer cells plays an important role in the inflammatory process resulting in alcoholic hepatitis. There is no effective treatment for AH, although notable progress has been made over the last decade in understanding the underlying mechanism of alcoholic hepatitis. We specifically review the current research on the role of Kupffer cells in the pathogenesis of AH and the treatment strategies. We suggest that the imbalance between the pro-inflammatory and the anti-inflammatory process as well as the increased production of reactive oxygen species eventually lead to hepatocyte injury, the final event of alcoholic hepatitis.

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Perforin and granzyme B lytic protein expression during chronic viral and autoimmune hepatitis

Cited by 53 publications

References 35 publications

Blockade of the Fas/Fas ligand interaction suppresses hepatocyte apoptosis in ischemia-reperfusion rat liver

Blockade of the Fas/Fas ligand interaction suppresses hepatocyte apoptosis in ischemia-reperfusion rat liver

Cryptococcus neoformansDirectly Stimulates Perforin Production and Rearms NK Cells for Enhanced Anticryptococcal Microbicidal Activity

Alcoholic hepatitis: The pivotal role of Kupffer cells

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