Kinetics of lipopolysaccharide clearance by Kupffer and parenchyma cells in perfused rat liver

Bikhazi, Anwar B.; Jurjus, Abdo; Kamal, Maud; Al-Housseini, Ali M; Saab, Rola Nazih; Jaroudi, Wael Al; Bitar, Khalil M.

doi:10.1016/s1532-0456(01)00207-1

Cited by 19 publications

(17 citation statements)

References 18 publications

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“…An in vivo study using gadolinium chloride indicates an important role of Kupffer cells in the clearance of endotoxin in endotoxemic rats (21). LPS clearance is regulated by apical-sinusoidal endocytic pathways, as well as canalicular routes, in the liver (22). The present results obtained from in vivo experiments showed that Ͼ50% of [ 3 H]lipid A accumulated in the liver 30 min after the retro-orbital plexus injection of lipid A (see Fig.…”

Section: Discussionsupporting

confidence: 57%

Mannose-Binding Lectin Augments the Uptake of Lipid A, Staphylococcus aureus, and Escherichia coli by Kupffer Cells through Increased Cell Surface Expression of Scavenger Receptor A

Ono

Nishitani

Mitsuzawa

et al. 2006

The Journal of Immunology

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We investigated roles of scavenger receptor A (SR-A) and mannose-binding lectin (MBL) in the uptake of endotoxin and bacteria by Kupffer cells. When [3H]lipid A was injected into retro-orbital plexus of mice, significantly less accumulation of lipid A in the liver was observed in SR-A-deficient mice and wild-type mice coinjected with fucoidan or acetylated low-density lipoprotein, which are known ligands for SR-A. Isolated Kupffer cells were able to take up [3H]lipid A in a time-dependent manner. The amount of lipid A associated with nonadherent Kupffer cells derived from SR-A-deficient mice was reduced by ∼80% when compared with wild-type cells, indicating an important role of SR-A in endotoxin uptake by Kupffer cells. The lipid A uptake by Kupffer cells was significantly enhanced in the presence of rMBL. Coincubation of fucoidan with [3H]lipid A significantly inhibited the basal and the MBL-stimulated uptake of lipid A by Kupffer cells. Preincubation of MBL with Kupffer cells also increased the uptake of lipid A. These results indicate that MBL augments the SR-A-mediated uptake of lipid A by Kupffer cells. Consistently, the exposure of MBL to Kupffer cells increased cell surface SR-A expression. The phagocytosis of Staphylococcus aureus and Escherichia coli by Kupffer cells was also enhanced by preincubation of MBL with the cells. In addition, MBL bound to lipid A, LPS, and S. aureus, and precipitated S. aureus. This study demonstrates important roles of SR-A and MBL in the uptake of endotoxin and bacteria by Kupffer cells.

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Section: Discussionsupporting

confidence: 57%

Mannose-Binding Lectin Augments the Uptake of Lipid A, Staphylococcus aureus, and Escherichia coli by Kupffer Cells through Increased Cell Surface Expression of Scavenger Receptor A

Ono

Nishitani

Mitsuzawa

et al. 2006

The Journal of Immunology

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“…Our previous studies revealed that disturbance of intestinal microflora was observed in patients with CVH; the counts of Bifidobacterium were significantly decreased, whereas the numbers of Enterococcus were increased. 3,18,22 We found in this study that the plasma endotoxin was decreased slightly under routine therapy in CH patients, but no significant change in intestinal microflora was found. The result indicated that with the recovery of the liver function, the hepatic Kupffer cells' capacity for endotoxin clearance was restored to some extent, 23,24 leading to the decrease of plasma endotoxin levels.…”

Section: Discussionmentioning

confidence: 52%

Effects of lactitol on intestinal microflora and plasma endotoxin in patients with chronic viral hepatitis

Chen

Wang

et al. 2007

Journal of Infection

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“…LPS clearance by the liver was initially studied over 20 years ago, and uptake of LPS has previously been shown to occur in both hepatocytes and Kupffer cells (45). We now show that pure isolated hepatocytes are able to take up LPS.…”

Section: Discussionmentioning

confidence: 53%

β2-Integrin-induced p38 MAPK Activation Is a Key Mediator in the CD14/TLR4/MD2-dependent Uptake of Lipopolysaccharide by Hepatocytes

Scott

Billiar

2008

Journal of Biological Chemistry

113

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The liver is the main organ that clears circulating lipopolysaccharide (LPS), and hepatocytes are a major cell type involved in LPS uptake. Little is known about the mechanisms for LPS internalization in hepatocytes and what signaling pathways are involved. We show here that LPS uptake is initiated after formation of a multi-receptor complex within lipid rafts. We find that essential components for LPS uptake are CD14, TLR4, MD2, and the ␤2-integrin CD11b/CD18. Activation of p38 MAPK is also essential for the initiation of LPS uptake, and interestingly, we show that this activation is not through TLR4 signaling by MyD88 but through activation of TIRAP via CD11b/CD18. However, TLR4/MD2 remain essential components at the cell surface as part of the LPS receptor complex. We therefore suggest novel roles for TLR4/MD2, CD11b/CD18, TIRAP, and p38 MAPK in LPS uptake by hepatocytes.The liver is the first major organ downstream of the gut and is responsible for the clearance and initial recognition of the majority of LPS 2 (1). Studies using radiolabeled LPS characterized the uptake and processing of LPS within the liver more than 20 years ago (2, 3). LPS is taken up by both parenchymal cells (hepatocytes) and nonparenchymal cells (Kupffer cells, hepatic stellate cells, etc.) in the liver, and it appears in the bile within 15 min of intravenous injection (4). Controversy remains regarding the relative roles of Kupffer cells and hepatocytes in the uptake and clearance of LPS. Kupffer cells rapidly produce a strong cytokine response to LPS (5) and can deacylate LPS using a lipase (6). Another study suggested that some types of LPS are preferentially taken up by Kupffer cells and deacylated, which then allows for more rapid internalization within hepatocytes (7). However other studies using gadolinium chloride to deplete Kupffer cells have determined that hepatocytes also play a major role in LPS clearance (4). Regardless, it is clear that hepatocytes, which form the largest mass of cells in the liver and are constantly exposed to endotoxin from the gut, play an important role in LPS uptake, and innate immune responses to LPS are dependent on this process.The mechanisms involved in the internalization of LPS remain poorly understood, however. Our laboratory has previously shown that hepatocytes express the cell surface components of the LPS receptor/signaling complex (CD14/TLR4/ MD2) (8 -10) and that signaling activated by LPS through this receptor complex on hepatocytes leads to the activation of MAPK signaling proteins, translocation of NFB to the nucleus, and also production and release of acute phase proteins such as soluble CD14 and LPS-binding protein (8, 9). However, the functional role of the LPS recognition complex on hepatocytes remains uncertain. Here we hypothesize that this complex plays a role in the binding and initiation of uptake of LPS into cells.In this study we have clarified the mechanism of initial uptake of LPS into primary isolated hepatocytes. As expected, we found that CD14, MD2, and TLR4 were requ...

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Kinetics of lipopolysaccharide clearance by Kupffer and parenchyma cells in perfused rat liver

Cited by 19 publications

References 18 publications

Mannose-Binding Lectin Augments the Uptake of Lipid A, Staphylococcus aureus, and Escherichia coli by Kupffer Cells through Increased Cell Surface Expression of Scavenger Receptor A

Mannose-Binding Lectin Augments the Uptake of Lipid A, Staphylococcus aureus, and Escherichia coli by Kupffer Cells through Increased Cell Surface Expression of Scavenger Receptor A

Effects of lactitol on intestinal microflora and plasma endotoxin in patients with chronic viral hepatitis

β2-Integrin-induced p38 MAPK Activation Is a Key Mediator in the CD14/TLR4/MD2-dependent Uptake of Lipopolysaccharide by Hepatocytes

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