Old and new findings on lipopolysaccharide-binding protein: a soluble pattern-recognition molecule

Schumann, Ralf R.

doi:10.1042/bst0390989

Cited by 127 publications

(123 citation statements)

References 95 publications

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“…Moreover, we found that the LBP-MetS association was more pronounced in normal-weight participants than in overweight and obese individuals. Since its discovery in the 1980s, LBP has been considered a key protein in mediating LPS-triggered innate immunity in a CD14-and TLR4-dependent manner [7,20]. As a surrogate marker of LPS, circulating LBP concentration was shown to be positively associated with prevalence of MetS in our previous overweight/obese case-control analysis [9].…”

Section: Discussionmentioning

confidence: 69%

“…However, owing to its short half-life and interference in the blood, it is difficult to measure circulating LPS in large-scale population-based studies [6]. By contrast, lipopolysaccharide binding protein (LBP), which is mainly synthesised in the liver, could specifically bind to and monomerise exogenous LPS, thereafter enabling the endotoxin to be recognised by Toll-like receptor 4 (TLR4) and cluster of differentiation 14 (CD14), which are responsible for consequent innate immunity [7]. Therefore, circulating LBP levels, with a relatively long half-life, have been used as a variable to assess endotoxaemia status and its immune responses [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Lipopolysaccharide binding protein, obesity status and incidence of metabolic syndrome: a prospective study among middle-aged and older Chinese

Liu

Pang

et al. 2014

Diabetologia

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Aims/hypothesis Although microbiota-derived endotoxaemia has previously been shown to induce metabolic disorders, data from population-based longitudinal studies are scarce. This study therefore investigated the associations between lipopolysaccharide binding protein (LBP) levels and 6 year incident metabolic syndrome (MetS), as well as the potentially modifying effects of obesity status in middle-aged and older Chinese men and women. Methods A total of 2,529 men and women aged 50-70 years from Beijing and Shanghai, China, were followed for 6 years. Those free of MetS at baseline (1,312) were included in the analyses for the risk of developing MetS. Baseline plasma LBP was measured using an ELISA kit.Results During the 6 year follow-up, 449 (34.2%) participants developed MetS. Baseline LBP was significantly associated with BMI, waist circumference, blood lipid profile and C-reactive protein (CRP) both at baseline and during follow-up (all p<0.05). The RR for incident MetS comparing extreme quartiles of LBP was 1.28 (95% CI 1.04, 1.58), after multivariate adjustment including BMI and CRP. In stratified analysis, LBP was positively associated with incident MetS only in normal-weight participants (RR, comparing extreme tertiles, 1.59; 95% CI 1.18, 2.15; p trend =0.002), but not in their overweight/obese counterparts (RR, comparing extreme tertiles, 0.99; 95% CI 0.80, 1.22; p trend =0.880). A significant interaction was observed between LBP and obesity status ( p interaction =0.013). Conclusions/interpretation Our study suggested that elevated plasma LBP was associated with an increased risk of developing MetS among middle-aged and older Chinese, especially in normal-weight individuals.

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Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide binding protein, obesity status and incidence of metabolic syndrome: a prospective study among middle-aged and older Chinese

Liu

Pang

et al. 2014

Diabetologia

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“…Lipid A interacts with almost all host cells but has been investigated mainly in relation to monocytes and macrophages (184). LPS-binding protein (LBP), a soluble acute-phase protein, binds LPS and shuttles it to the membrane-bound CD-14 receptor (185). The CD-14 receptor facilitates transfer to the TLR-4/MD-2 receptor complex.…”

Section: Fig 6 O-antigen Lps Biosynthesis and Lps Assembly And Transpmentioning

confidence: 99%

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

Tytgat

Lebeer

2014

Microbiol Mol Biol Rev

128

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SUMMARY Humans have been increasingly recognized as being superorganisms, living in close contact with a microbiota on all their mucosal surfaces. However, most studies on the human microbiota have focused on gaining comprehensive insights into the composition of the microbiota under different health conditions (e.g., enterotypes), while there is also a need for detailed knowledge of the different molecules that mediate interactions with the host. Glycoconjugates are an interesting class of molecules for detailed studies, as they form a strain-specific barcode on the surface of bacteria, mediating specific interactions with the host. Strikingly, most glycoconjugates are synthesized by similar biosynthesis mechanisms. Bacteria can produce their major glycoconjugates by using a sequential or an en bloc mechanism, with both mechanistic options coexisting in many species for different macromolecules. In this review, these common themes are conceptualized and illustrated for all major classes of known bacterial glycoconjugates, with a special focus on the rather recently emergent field of glycosylated proteins. We describe the biosynthesis and importance of glycoconjugates in both pathogenic and beneficial bacteria and in both Gram-positive and -negative organisms. The focus lies on microorganisms important for human physiology. In addition, the potential for a better knowledge of bacterial glycoconjugates in the emerging field of glycoengineering and other perspectives is discussed.

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“…In CD14-positive cells (e.g., macrophages), TLR4 is internalized in endosomes where it dissociates from MyD88 and interacts with TRIF to activate IRF3 (7,12). LBP belongs to a LBP/bactericidal/permeability-increasing protein/palate, lung and nasal epithelial clone protein superfamily and is produced primarily in liver and epithelial cells of the lungs and gastrointestinal tract as an acute phase serum glycoprotein (25). The family members constitute physical barriers against bacterial infection in innate immunity (25,26).…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide (LPS)-binding protein stimulates CD14-dependent Toll-like receptor 4 internalization and LPS-induced TBK1–IKKϵ–IRF3 axis activation

Tsukamoto

Takeuchi

Kubota

et al. 2018

Journal of Biological Chemistry

139

101

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(HT) † These authors contributed equally to this work. Running title: LBP mediates LPS-induced TLR4 internalization and signalingKeywords: CD14, cell surface receptor, endotoxin, innate immunity, LPS, LPS-binding protein (LBP), pathogen-associated molecular pattern (PAMP), pattern recognition receptor (PRR), TIR-domaincontaining adapter-inducing interferon-β (TRIF), Toll-like receptor 4 (TLR4), AbstractToll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the cell surface and becomes internalized in an endosome. However, the spatial regulation of TLR4 signaling is not fully understood. Here, we investigated the mechanisms of LPS-induced TLR4 internalization and clarified the roles of the extracellular LPS-binding molecules, LPS-binding protein (LBP), and glycerophosphatidylinositol-anchored protein (CD14). LPS stimulation of CD14-expressing cells induced TLR4 internalization in the presence of serum, and an inhibitory anti-LBP mAb blocked its internalization. Addition of LBP to serum-free cultures restored LPS-induced TLR4 internalization to comparable levels of serum. The secretory form of the CD14 (sCD14) induced internalization but required a much higher concentration than LBP. An inhibitory anti-sCD14 mAb was ineffective for serum-mediated internalization. LBP lacking the domain for LPS transfer to CD14 and a CD14 mutant with reduced LPS binding both attenuated TLR4 internalization. Accordingly, LBP is an essential serum molecule for TLR4 internalization, and its LPS transfer to membrane-anchored CD14 (mCD14) is a prerequisite. LBP induced the LPS-stimulated phosphorylation of TBK1, IKKε, and IRF3, leading to IFN-β expression. However, LPS-stimulated late activation of NFκB or necroptosis were not affected. Collectively, our results indicate that LBP controls LPS-induced TLR4 internalization, which induces LBP mediates LPS-induced TLR4 internalization and signaling 1 http://www.jbc.org/cgi

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Old and new findings on lipopolysaccharide-binding protein: a soluble pattern-recognition molecule

Cited by 127 publications

References 95 publications

Lipopolysaccharide binding protein, obesity status and incidence of metabolic syndrome: a prospective study among middle-aged and older Chinese

Lipopolysaccharide binding protein, obesity status and incidence of metabolic syndrome: a prospective study among middle-aged and older Chinese

The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates

Lipopolysaccharide (LPS)-binding protein stimulates CD14-dependent Toll-like receptor 4 internalization and LPS-induced TBK1–IKKϵ–IRF3 axis activation

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