Phagocytosis and LPS‐stimulated production of cytokines and prostaglandin E2 is different in Kupffer cells isolated from the periportal or perivenous liver region

Bykov, Igor; Ylipaasto, Petri; Eerola, Leena I.; Lindros, Kai O.

doi:10.1080/00365520310007116

Cited by 18 publications

(10 citation statements)

References 19 publications

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“…LPS absorption in macrophages and other cells is increased under pathophysiological conditions [7]. LPS induces cellular toxicity by involving inflammatory cells and chemical mediators such as reactive oxygen species (ROS), reactive nitrogen species (RNS), pro-inflammatory cytokines and prostaglandins (PGs) [8], [9]. Acetylsalicylic acid (ASA, aspirin), a specific inhibitor of cyclooxygenase (COX) enzyme and a commonly used anti-inflammatory drug, has multiple pharmacological effects which may not be associated with its COX inhibitory activity [10], [11].…”

Section: Introductionmentioning

confidence: 99%

NAC Attenuates LPS-Induced Toxicity in Aspirin-Sensitized Mouse Macrophages via Suppression of Oxidative Stress and Mitochondrial Dysfunction

2014

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Bacterial endotoxin lipopolysaccharide (LPS) induces the production of inflammatory cytokines and reactive oxygen species (ROS) under in vivo and in vitro conditions. Acetylsalicylic acid (ASA, aspirin) is a commonly used anti-inflammatory drug. Our aim was to study the effects of N-acetyl cysteine (NAC), an antioxidant precursor of GSH synthesis, on aspirin-sensitized macrophages treated with LPS. We investigated the effects of LPS alone and in conjunction with a sub-toxic concentration of ASA, on metabolic and oxidative stress, apoptosis, and mitochondrial function using J774.2 mouse macrophage cell line. Protection from LPS-induced toxicity by NAC was also studied. LPS alone markedly induced ROS production and oxidative stress in macrophage cells. When ASA was added to LPS-treated macrophages, the increase in oxidative stress was significantly higher than that with LPS alone. Similarly, alteration in glutathione-dependent redox metabolism was also observed in macrophages after treatment with LPS and ASA. The combination of LPS and ASA selectively altered the CYP 3A4, CYP 2E1 and CYP 1A1 catalytic activities. Mitochondrial respiratory complexes and ATP production were also inhibited by LPS-ASA treatment. Furthermore a higher apoptotic cell death was also observed in LPS-ASA treated macrophages. NAC pre-treatment showed protection against oxidative stress induced apoptosis and mitochondrial dysfunction. These effects are presumed, at least in part, to be associated with alterations in NF-κB/Nrf-2 mediated cell signaling. These results suggest that macrophages are more sensitive to LPS when challenged with ASA and that NAC pre-treatment protects the macrophages from these deleterious effects.

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Section: Introductionmentioning

confidence: 99%

NAC Attenuates LPS-Induced Toxicity in Aspirin-Sensitized Mouse Macrophages via Suppression of Oxidative Stress and Mitochondrial Dysfunction

2014

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“…Liver macrophages are well known for functional heterogeneity 4,6,7,9,13 . Accordingly, different sizes of hepatic macrophages isolated from rat livers have been discussed in the literature 7,12,32 . There was also description of zonal distribution of KCs 4 .…”

Section: Discussionmentioning

confidence: 99%

“…4,6,7,9,13 Accordingly, different sizes of hepatic macrophages isolated from rat livers have been discussed in the literature. 7,12,32 There was also description of zonal distribution of KCs. 4 The large ED1 + /ED2 + KCs are located in the liver along the sinusoids while the small ED1 + /ED2 -KCs are found mainly located around the central vein and portal vessels.…”

Section: Differential Expression Of Mrna For Cytokines Ecm Remodelinmentioning

confidence: 99%

Flow cytometric isolation and phenotypic characterization of two subsets of ED2⁺ (CD163) hepatic macrophages in rats

Sadahiro

Noh

et al. 2009

Hepatology Research

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“…They are larger and twice as populous in periportal than in centrilobular regions, have more active lysosomes and greater phagocytic activity; however, they secrete fewer superoxide anions. 25,32 Their progenitors are monocytes from the bone marrow which enter the systemic circulation and reach the hepatic tissue, but they also possess the ability for self-renewal. 33,34 Experiments on rodent and human tissue demonstrated that their life span appears to vary from several weeks to one year.…”

Section: K Cs Were Named After Carl Von Kupffer Thementioning

confidence: 99%

Role of Kupffer cells in the outgrowth of colorectal cancer liver metastases

Paschos

Majeed

Bird

2010

Hepatology Research

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Colorectal cancer is one of the commonest malignancies in the "developed" world. The liver constitutes the main host organ for its distant metastases which, when present, augur a bad prognosis for the disease. Kupffer cells (KCs) are macrophages that constantly reside within the liver and form an effective first line defence against multiple harmful agents which reach the hepatic sinusoids via the portal circulation. KCs remove chemical compounds and dead or damaged cells, eliminate bacteria and protect against invading tumour cells. They may play a crucial tumouricidal role, exerting cytotoxic and cytostatic functions through the release of multiple cytokines and chemokines. Subsequently, colorectal metastasising cells are destroyed either by KC-performed phagocytosis or via the stimulation of other immune cells which migrate into the sinusoids and act accordingly. On the contrary, KC products, including cytokines, growth factors and matrix-degrading enzymes may promote liver metastasis, supporting tumour cell extravasation, motility and invasion. Current research aims to exploit the antineoplastic properties of KCs in new therapeutic approaches of colorectal cancer liver metastasis. Numerous agents, such as the granulocyte macrophage-colony stimulating factor, interferon gamma, muramyl peptide analogues and various antibody based treatments, have been tested in experimental models with promising results. Future trials may investigate their use in everyday clinical practice and compare their therapeutic value with current treatment of the disease.

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Phagocytosis and LPS‐stimulated production of cytokines and prostaglandin E2 is different in Kupffer cells isolated from the periportal or perivenous liver region

Cited by 18 publications

References 19 publications

NAC Attenuates LPS-Induced Toxicity in Aspirin-Sensitized Mouse Macrophages via Suppression of Oxidative Stress and Mitochondrial Dysfunction

NAC Attenuates LPS-Induced Toxicity in Aspirin-Sensitized Mouse Macrophages via Suppression of Oxidative Stress and Mitochondrial Dysfunction

Flow cytometric isolation and phenotypic characterization of two subsets of ED2⁺ (CD163) hepatic macrophages in rats

Role of Kupffer cells in the outgrowth of colorectal cancer liver metastases

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Phagocytosis and LPS‐stimulated production of cytokines and prostaglandin E2 is different in Kupffer cells isolated from the periportal or perivenous liver region

Cited by 18 publications

References 19 publications

NAC Attenuates LPS-Induced Toxicity in Aspirin-Sensitized Mouse Macrophages via Suppression of Oxidative Stress and Mitochondrial Dysfunction

NAC Attenuates LPS-Induced Toxicity in Aspirin-Sensitized Mouse Macrophages via Suppression of Oxidative Stress and Mitochondrial Dysfunction

Flow cytometric isolation and phenotypic characterization of two subsets of ED2+ (CD163) hepatic macrophages in rats

Role of Kupffer cells in the outgrowth of colorectal cancer liver metastases

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Flow cytometric isolation and phenotypic characterization of two subsets of ED2⁺ (CD163) hepatic macrophages in rats