Binding of lipopolysaccharide (LPS) to CHO cells does not correlate with LPS-induced NF-κB activation

Hamann, Lutz; Schumann, Ralf R.; Flad, Hans‐Dieter; Brade, Lore; Rietschel, Ernst; Ulmer, Artur J.

doi:10.1002/1521-4141(200001)30:1<211::aid-immu211>3.0.co;2-o

Cited by 13 publications

(2 citation statements)

References 19 publications

(27 reference statements)

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“…We and others have proposed a "silent uptake" of LPS that potentially is mediated by higher concentrations of LBP. 41,42 Recent observations by us suggest that these cellular mechanisms may occur both CD14-dependently and CD14-independently (unpublished results, 2001), which is in line with recent observations by others on CD14-independent effects of Gram-negative bacteria and LPS. [43][44][45] We demonstrate here that acute-phase sera of severe sepsis patients are able to reduce LPS binding to monocytes and their subsequent activation.…”

Section: Discussionsupporting

confidence: 81%

High concentrations of lipopolysaccharide-binding protein in serum of patients with severe sepsis or septic shock inhibit the lipopolysaccharide response in human monocytes

Zweigner

Gramm

Singer

et al. 2001

Blood

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214

162

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Lipopolysaccharide-binding protein (LBP), an acute-phase protein recognizing lipopolysaccharide (LPS), catalyzes in low concentrations its transfer to the cellular LPS receptor consisting of CD14 and Toll-like receptor-4. It has recently been shown that high concentrations of recombinant LBP can protect mice in a peritonitis model from the lethal effects of LPS. To determine whether in humans the acute-phase rise of LBP concentrations can inhibit LPS binding to monocytes and induction of proinflammatory cytokines, LBP concentrations were analyzed in 63 patients meeting the American College of Chest Physicians/Society of Critical Care Medicine criteria of severe sepsis or septic shock and the ability of these sera to modulate LPS effects in vitro was assessed employing different assays. Transfer of fluorescein isothiocyanate-labeled LPS to human monocytes was assessed by a fluorescence-activated cell sorter-based method, and activation of monocytes was investigated by measuring LPS-induced tumor necrosis factor-alpha secretion in the presence of the sera. Anti-LBP antibodies and recombinant human LBP were instrumental for depletion and reconstitution of acute-phase sera and subsequent assessment of their modulating effects on LPS activity. Sera of patients with severe sepsis/septic shock exhibited a diminished LPS transfer activity and LPS-induced tumor necrosis factor-alpha secretion as compared with sera from healthy controls. LBP depletion of sepsis sera and addition of rhLBP resulting in concentrations found in severe sepsis confirmed that LBP was the major serum component responsible for the observed effects. In summary, the inhibition of LPS effects by high concentrations of LBP in acute-phase serum, as described here, may represent a novel defense mechanism of the host in severe sepsis and during bacterial infections.

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Section: Discussionsupporting

confidence: 81%

High concentrations of lipopolysaccharide-binding protein in serum of patients with severe sepsis or septic shock inhibit the lipopolysaccharide response in human monocytes

Zweigner

Gramm

Singer

et al. 2001

Blood

Self Cite

214

162

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“…The preparation of nuclear extracts and electrophoretic mobility shift assay (EMSA) was performed as described elsewhere (25). Briefly, we used 7.5 fmol γ‐[ 32 P]dATP‐labeled oligonucleotides containing the NFκB binding sequence and 4 µg of crude nuclear extract in the DNA binding reaction.…”

Section: Methodsmentioning

confidence: 99%

The LPS receptor (CD14) links innate immunity with Alzheimer's disease

et al. 2003

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To rapidly respond to invading microorganisms, humans call on their innate immune system. This occurs by microbe-detecting receptors, such as CD14, that activate immune cells to eliminate the pathogens. Here, we link the lipopolysaccharide receptor CD14 with Alzheimer`s disease, a severe neurodegenerative disease resulting in dementia. We demonstrate that this key innate immunity receptor interacts with fibrils of Alzheimer amyloid peptide. Neutralization with antibodies against CD14 and genetic deficiency for this receptor significantly reduced amyloid peptide induced microglial activation and microglial toxicity. The observation of strongly enhanced microglial expression of the LPS receptor in brains of animal models of Alzheimer's disease indicates a clinical relevance of these findings. These data suggest that CD14 may significantly contribute to the overall neuroinflammatory response to amyloid peptide, highlighting the possibility that the enormous progress currently being made in the field of innate immunity could be extended to research on Alzheimer's disease.

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Pattern Recognition

Schröder

Schumann

2010

Topley &Amp; Wilson's Microbiology and Microbial Infections

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Binding of lipopolysaccharide (LPS) to CHO cells does not correlate with LPS-induced NF-κB activation

Cited by 13 publications

References 19 publications

High concentrations of lipopolysaccharide-binding protein in serum of patients with severe sepsis or septic shock inhibit the lipopolysaccharide response in human monocytes

High concentrations of lipopolysaccharide-binding protein in serum of patients with severe sepsis or septic shock inhibit the lipopolysaccharide response in human monocytes

The LPS receptor (CD14) links innate immunity with Alzheimer's disease

Pattern Recognition

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