Scavenger receptor pathway for lipopolysaccharide binding to Kupffer and endothelial liver cells in vitro

Shnyra, Alexander; Lindberg, Annelie

doi:10.1128/iai.63.3.865-873.1995

Cited by 56 publications

(24 citation statements)

References 26 publications

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“…The idea that reticuloendothelial cells function as a back-up or scavenger system for the removal of circulating LPS is supported by data showing that the scavenger receptor is responsible for the binding of LPS by Kupffer cells. 88 Because our model employs a smaller, more relevant dose of LPS, we believe hepatocytes are more likely to play a major role in its catabolism than generally believed, especially under typical physiological conditions.…”

Section: Discussionmentioning

confidence: 97%

Chylomicrons alter the hepatic distribution and cellular response to endotoxin in rats

1998

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Sepsis caused by gram-negative bacterial infection is an important and frequently devastating problem, annually affecting approximately 500,000 patients 1 and causing over 150,000 deaths. 2-6 While the incidence of sepsis has more than doubled during the last quarter century, 7 there has not been a substantial improvement in the survival rate since the 1970s. 8,9 Even though there are many effective antibiotics, they are often unsuccessful as the sole mode of therapy.

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Section: Discussionmentioning

confidence: 97%

Chylomicrons alter the hepatic distribution and cellular response to endotoxin in rats

1998

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“…Anti-LBP (mAb 2B5; 20 µg/ml) or anti-CD14 (mAb 28C5; 20 µg/ml) was added to cells 30 min before LPS. 32 P-labeled LBP (250 ng/ml) was incubated with the cells either with LPS (10 ng/ml), sCD14 (160 ng/ml), or anti-LBP (mAb 2B5; 20 µg/ml) (C). After 2 h, cells were treated with 250 µg/ml proteinase K for 30 min, harvested, washed twice, and lysed, and the counts were assayed in scintillation fluid.…”

Section: Discussionmentioning

confidence: 99%

“…After 2 h, cells were treated with 250 µg/ml proteinase K for 30 min, harvested, washed twice, and lysed, and the counts were assayed in scintillation fluid. Data are given as means ± SE of 3 H activity or 32 9. LBP-stimulated LPS uptake into HCAEC involves a scavenger receptor pathway.…”

Section: Discussionmentioning

confidence: 99%

Toll‐like receptor 4 functions intracellularly in human coronary artery endothelial cells: roles of LBP and sCD14 in mediating LPS‐responses

et al. 2004

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Endothelial cells are activated by microbial agonists through Toll-like receptors (TLRs) to express inflammatory mediators; this is of significance in acute as well as chronic inflammatory states such as septic shock and atherosclerosis, respectively. We investigated mechanisms of lipopolysaccharide (LPS)-induced cell activation in human coronary artery endothelial cells (HCAEC) using a combination of FACS, confocal microscopy, RT-PCR, and functional assays. We found that TLR4, in contrast to TLR2, is not only located intracellularly but also functions intracellularly. That being the case, internalization of LPS is required for activation. We further characterized the HCAEC LPS uptake system and found that HCAEC exhibit an effective LPS uptake only in the presence of LPS binding protein (LBP). In addition to its function as a catalyst for LPS-CD14 complex formation, LBP enables HCAEC activation at low LPS concentrations by facilitating the uptake, and therefore delivery, of LPS-CD14 complexes to intracellular TLR4-MD-2. LBP-dependent uptake involves a scavenger receptor pathway. Our findings may be of pathophysiological relevance in the initial response of the organism to infection. Results further suggest that LBP levels, which vary as LBP is an acute phase reactant, could be relevant to initiating inflammatory responses in the vasculature in response to chronic or recurring low LPS.

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“…Many proinflammatory, adhesion-promoting substances are physiologically present in portal venous blood (bacterial antigens, LPS etc.) and are cleared by Kupffer cells and LSEC (27). Kupffer cells as well as LSEC show a normal inflammatory reaction to LPS in vitro with increased expression of CD54/106 (A. Uhrig, R. Banafsche, M. König, S. Hegenbarth, G. Gerken, P. A. Knolle, manuscript in preparation).…”

Section: The Hepatic Microcirculation and Antigen-non-specific Leukocmentioning

confidence: 99%

Local control of the immune response in the liver

Knolle

Gerken

2000

Immunological Reviews

550

420

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The physiological function of the liver--such as removal of pathogens and antigens from the blood, protein synthesis and metabolism--requires an immune response that is adapted to these tasks and is locally regulated. Pathogenic microorganisms must be efficiently eliminated while the large number of antigens derived from the gastrointestinal tract must be tolerized. From experimental observations it is evident that the liver favours the induction of tolerance rather than the induction of immunity. The liver probably not only is involved in transplantation tolerance but contributes as well to tolerance to orally ingested antigens (entering the liver with portal-venous blood) and to containment of systemic immune responses (antigen from the systemic circulation entering the liver with arterial blood). This review summarizes the experimental data that shed light on the molecular mechanisms and the cell populations of the liver involved in local immune regulation in the liver. Although hepatocytes constitute the major cell population of the liver, direct interaction of hepatocytes with leukocytes in the blood is unlikely. Sinusoidal endothelial cells, which line the hepatic sinusoids and separate hepatocytes from leukocytes in the sinusoidal lumen, and Kupffer cells, the resident macrophage population of the liver, can directly interact with passenger leukocytes. In the liver, clearance of antigen from the blood occurs mainly by sinusoidal endothelial cells through very efficient receptor-mediated endocytosis. Liver sinusoidal endothelial cells constitutively express all molecules necessary for antigen presentation (CD54, CD80, CD86, MHC class I and class II and CD40) and can function as antigen-presenting cells for CD4+ and CD8+ T cells. Thus, these cells probably contribute to hepatic immune surveillance by activation of effector T cells. Antigen-specific T-cell activation is influenced by the local microenvironment. This microenvironment is characterized by the physiological presence of bacterial constituents such as endotoxin and by the local release of immunosuppressive mediators such as interleukin-10, prostaglandin E2 and transforming growth factor-beta. Different hepatic cell populations may contribute in different ways to tolerance induction in the liver. In vitro experiments revealed that naive T cells are activated by resident sinusoidal endothelial cells but do not differentiate into effector T cells. These T cells show a cytokine profile and a functional phenotype that is compatible with the induction of tolerance. Besides sinusoidal endothelial cells, other cell populations of the liver, such as dendritic cells, Kupffer cells and perhaps also hepatocytes, may contribute to tolerance induction by deletion of T cells through induction of apoptosis.

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Scavenger receptor pathway for lipopolysaccharide binding to Kupffer and endothelial liver cells in vitro

Cited by 56 publications

References 26 publications

Chylomicrons alter the hepatic distribution and cellular response to endotoxin in rats

Chylomicrons alter the hepatic distribution and cellular response to endotoxin in rats

Toll‐like receptor 4 functions intracellularly in human coronary artery endothelial cells: roles of LBP and sCD14 in mediating LPS‐responses

Local control of the immune response in the liver

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