Disease relevance of Lbp

• To investigate the specific role of LBP in LPS activation of Kupffer cells, we produced a functional recombinant rat LBP using a baculovirus expression system, which we used to selectively examine the role of LBP's on Kupffer-cell function [1].
• The role of lipopolysaccharide binding protein in resistance to Salmonella infections in mice [2].
• Here we report that LBP KO mice are more susceptible to Salmonella peritonitis, but not to oral or i.v. infection [2].
• LBP knockout (KO) mice responded normally to i.p. injections of Staphylococcus aureus and casein, but not to i.p. injection of S. typhimurium or Salmonella LPS [2].
• OBJECTIVE: To study the potential roles of lipopolysaccharide (LPS) signaling molecules, LPS-binding protein (LBP), CD14, and Toll-like receptor 4 (TLR4) in mice with acute necrotizing pancreatitis (ANP) [3].

Psychiatry related information on Lbp

• RESULTS: Decreased levels of serum AGE, hydroxyproline concentration in mouse skin and spontaneous motor activity in D-galactose mouse aging model were detected after treated with ABP or LBP, while lymphocyte proliferation and IL-2 activity, learning and memory abilities, SOD activity of erythrocytes, were enhanced [4].

High impact information on Lbp

• Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection [5].
• We propose the iterative anionic groups along the glycan backbone of the cell wall are a crucial structure for recognition by LBP [6].
• LBP was present in the CSF of patients with meningitis, and LBP-deficient mice failed to develop meningeal inflammation [6].
• Despite these striking in vitro findings, no significant differences in TNF-alpha levels were observed in plasma from wild-type and LBP-deficient mice injected with LPS [7].
• The role of LBP in promoting LPS responsiveness in vivo was tested in LBP-deficient mice produced by gene targeting in embryonic stem cells [7].

Chemical compound and disease context of Lbp

• Therefore, in this study, a long-term intragastric ethanol feeding model was used to test the hypothesis that LBP is involved in alcoholic hepatitis by comparing LBP knockout and wild-type mice [8].
• In conclusion, LBP KO mice are protected from toxicity with a decrease in hepatic necrosis following acetaminophen challenge [9].
• Thus, LBP appears to participate in the development of Ag-induced airway reactivity and peroxynitrite production, but does not seem to be required for the development of pulmonary inflammation [10].
• LBP(-/-) mice had less liver injury and fibrosis (Siruis red staining and hydroxyproline content) compared with wild-type mice after bile duct ligation [11].
• Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guérin produce a heparin-binding hemagglutinin adhesin (HBHA) required for extrapulmonary dissemination and a laminin-binding protein (LBP) involved in cytoadherence through laminin recognition [12].

Biological context of Lbp

• Lipopolysaccharide (LPS) binding protein (LBP) is a key serum factor that mediates LPS activation of mononuclear cells [1].
• These data are consistent with the hypothesis that LBP plays an important role in early alcohol-induced liver injury by enhancing LPS-induced signal transduction, most likely in Kupffer cells [8].
• Using confocal microscopy, we show that the neutrophils which accumulate in CD14 and LBP null mice, albeit with delayed kinetics, are nevertheless fully capable of ingesting the bacteria [13].
• These results point to the essential role of LBP/CD14 in innate immunity against virulent bacteria [14].
• Immunized LBP-deficient mice did not develop substantial Ag-induced airway reactivity, whereas WT mice developed marked bronchoconstriction following aerosol Ag sensitization and challenge with methacholine [10].

Anatomical context of Lbp

• In the presence of LBP, 1/1,000 the concentration of LPS is sufficient to activate peripheral blood monocytes [1].
• Previous studies with Kupffer cells have shown a variable effect of serum on LPS activation of these cells and led to the conclusion that, unlike extrahepatic mononuclear cells, Kupffer cells do not respond to LPS in an LBP-dependent fashion [1].
• Polymorphonuclear leukocytes (PMN) and LPS-binding protein (LBP) are both components of the innate immune system [2].
• Here, we report that LBP also plays an essential role in the innate immune response to Gram-positive pneumococci, specifically to their major inflammatory component, pneumococcal cell wall (PCW) [6].
• LBP(-/-) mice were highly susceptible to E. coli peritonitis, as indicated by accelerated mortality, earlier bacterial dissemination to the blood, impaired bacterial clearance in the peritoneal cavity, and more severe remote organ damage [15].

Associations of Lbp with chemical compounds

• These pathological changes were reduced significantly in LBP knockout mice fed ethanol (score, 2.6 +/- 0.5) [8].
• Lipopolysaccharide-binding protein modulates acetaminophen-induced liver injury in mice [9].
• Similarly, production of NO synthase 2 protein and the NO catabolite peroxynitrite was dramatically higher in the lungs of WT mice following challenge compared with that in LBP-deficient mice [10].
• Its NH2-terminal sequence (XNPGLVARTTNKGLEYSAQE) and its molecular weight (approximately 60 kd) were determined and were proved to be highly homologous to human LBP [16].
• Tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, lipopolysaccharide binding protein (LBP) and CD14 mRNA (messenger ribonucleic acid) expression in mouse liver were determined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) analysis [17].

Regulatory relationships of Lbp

• The relative ability of different cationic peptides to block the binding of LPS to LBP correlated with their ability to block LPS-induced TNF-alpha production by the RAW 264.7 macrophage cell line [18].

Other interactions of Lbp

• Isolated Kupffer cells exposed to increasing concentrations of LPS (0, 1, 10 ng/mL) showed a dose-dependent increase in TNF-alpha production, which was augmented and accelerated by the presence of LBP [1].
• Kupffer cell activation by lipopolysaccharide in rats: role for lipopolysaccharide binding protein and toll-like receptor 4 [1].
• The expression of tumor necrosis factor (TNF)- alpha, interleukin (IL)-6, lipopolysaccharide binding protein (LBP) and CD14 mRNA, and NF-kappaB and IkappaB-alpha protein in mouse liver at different time points after BCG and LPS injection were measured using RT-PCR, immunohistochemistry and Western blotting analysis, respectively [19].
• Dietary alcohol significantly increased liver to body weight ratios and serum alanine aminotransferase levels in wild-type mice (189 +/- 31 U/L) over high-fat controls (24 +/- 7 U/L), effects which were blunted significantly in LBP knockout mice (60 +/- 17 U/L) [8].
• The proteasome as a lipopolysaccharide-binding protein in macrophages: differential effects of proteasome inhibition on lipopolysaccharide-induced signaling events [20].

Analytical, diagnostic and therapeutic context of Lbp

• The levels of LBP and CD14 mRNA in mouse liver were markedly upregulated after treatment with BCG and LPS, and treatment with BCG alone led to an increase in CD14 mRNA in mouse liver [19].
• LBP levels are markedly elevated in bronchoalveolar lavage fluids obtained from asthmatic subjects compared with those in normal controls [10].
• To assay baboon plasma LBP levels, an enzyme-linked immunosorbent assay with cross-reactive antibodies to human LBP was developed [16].
• In conclusion, hemorrhagic shock and resuscitation to mice cause severe, LBP-mediated hepatocellular damage [21].
• The identity was further verified by Western blotting with an antibody against the 67 kDa LBP [22].

References