Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the hepatitis B virus S protein results in the formation of a lipoprotein particle, the hepatitis B surface antigen (HBsAg). Such particles, produced in Saccharomyces cerevisiae, bind to the cell surface of monocytes through interaction with the lipopolysaccharide binding protein and the lipopolysaccharide receptor, CD14. This attachment is suggested to depend on the presence of charged phospholipids in the particles. In addition, such particles interfere with the lipopolysaccharide and interleukin-2-induced activation of monocytes. In the present study, it is reported that of three Saccharomyces cerevisiae-derived HBsAg preparations, two have a reduced capacity to bind to monocytes. A correlation with a reduced potential to inhibit the lipopolysaccharide-induced activation of monocytes and an increased potential to stimulate HBsAg-specific T-cell proliferation is observed. Surprisingly, differences in phospholipid content that might explain these observations, were not detected.
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PMID:Saccharomyces cerevisiae-derived HBsAg preparations differ in their attachment to monocytes, immune-suppressive potential, and T-cell immunogenicity. 1279 12

Bacterial sepsis and septic shock result from the overproduction of inflammatory mediators as a consequence of the interaction of the immune system with bacteria and bacterial wall constituents in the body. Bacterial cell wall constituents such as lipopolysaccharide, peptidoglycans, and lipoteichoic acid are particularly responsible for the deleterious effects of bacteria. These constituents interact in the body with a large number of proteins and receptors, and this interaction determines the eventual inflammatory effect of the compounds. Within the circulation bacterial constituents interact with proteins such as plasma lipoproteins and lipopolysaccharide binding protein. The interaction of the bacterial constituents with receptors on the surface of mononuclear cells is mainly responsible for the induction of proinflammatory mediators by the bacterial constituents. The role of individual receptors such as the toll-like receptors and CD14 in the induction of proinflammatory cytokines and adhesion molecules is discussed in detail. In addition, the roles of a number of other receptors that bind bacterial compounds such as scavenger receptors and their modulating role in inflammation are described. Finally, the therapies for the treatment of bacterial sepsis and septic shock are discussed in relation to the action of the aforementioned receptors and proteins.
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PMID:Receptors, mediators, and mechanisms involved in bacterial sepsis and septic shock. 1285 74

We report a comprehensive physicochemical characterization of a glycoglycerolipid from Mycoplasma fermentans, MfGl-II, in relation to its bioactivity and compared this with the respective behaviors of phosphatidylcholine (PC) and a bacterial glycolipid, lipopolysaccharide (LPS) from deep rough mutant Salmonella minnesota strain R595. The beta left arrow over right arrow alpha gel-to-liquid crystalline phase transition behavior of the hydrocarbon chains with Tc = 30 degrees C for MfGl-II as well as for LPS exhibits high similarity between the two glycolipids. A lipopolysaccharide-binding protein (LBP)-mediated incorporation into negatively charged liposomes is observed for both glycolipids. The determination of the supramolecular aggregate structure confirms the existence of a mixed unilamellar/cubic structure for MfGl-II, similar to that observed for the lipid A moiety of LPS. The biological data clearly show that MfGl-II is able to induce cytokines such as tumor necrosis factor-alpha (TNF-alpha) in human mononuclear cells, although to a significantly lower degree than LPS. In contrast, in the Limulus amebocyte lysate test, MfGl-II is completely inactive, and in the CHO reporter cell line it does not indicate any reactivity with the Toll-like receptors TLR-2 and -4, in contrast to control lipopeptides and LPS. These data confirm the applicability of our conformational concept of endotoxicity to nonlipid A structures: an amphiphilic molecule with a nonlamellar cubic aggregate structure corresponding to a conical conformation of the single molecules and a sufficiently high negative charge density in the backbone.
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PMID:Physicochemical characterization and biological activity of a glycoglycerolipid from Mycoplasma fermentans. 1286 3

Using the differential screening technique, a cDNA related to the mammalian family of lipid transfer/lipopolysaccharide-binding proteins was cloned from the Atlantic cod (Gadus morhua L.). The gene is an ortholog of a recently identified gene of rainbow trout (Oncorhynchus mykiss). Phylogenetic analyses suggest that teleost BPI/LBP are modern descendants of the ancestor of mammalian bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP), and a gene of the urochordate Ciona intestinalis is related to this gene family. Molecular modeling suggests that the structure of cod BPI/LBP is similar to mammalian BPI and LBP, while its highly basic character is similar to BPI. Cod BPI/LBP is constitutively expressed in head-kidney (HK) leukocytes. After intraperitoneal injection of bacterin high levels of cod BPI/LBP mRNA were detected also in peripheral blood cells and spleen, while moderate to low levels of transcript were found in heart, liver, gills, skin, brain, and intestine. We conclude that the patterns of charge and expression of cod BPI/LBP are more similar to mammalian BPI than to mammalian LBP.
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PMID:Cloning and analyses of a BPI/LBP cDNA of the Atlantic cod (Gadus morhua L.). 1469 17

The physicochemical characteristics and in vitro biological activity of various synthetic hexaacyl phospholipid dimers were compared with the respective behavior of bacterial endotoxins (lipopolysaccharide, LPS). The structural variations of the synthetic amphiphiles include different stereochemical (R,S) configurations about their ester- and amide-linkages for the acyl chains and differences in the length of the serine backbone spacer. The temperature of the gel to liquid crystalline phase transition of the acyl chains (T(c)) lies between 10 and 15 degrees C for the compounds with the shortest backbone and decreases rapidly for the compounds with longer backbones. The phase transition enthalpies (8-16 kJ x mol(-1)) are considerably lower than those of lipid A from hexaacyl endotoxins (28-35 kJ x mol(-1)). In contrast, the dependence of T(c) on Mg(2+) and water content shows a behavior typical for endotoxins: a significant increase with increasing Mg(2+) and decreasing water concentrations. The aggregate structure is sensitively dependent not only on the length of the backbone spacer but also on the different stereochemical variations. It can be directly correlated with the biological activity of the compounds. Thus, as with natural lipid A, the capacity to induce cytokine production in mononuclear cells is directly related to the affinity to form nonlamellar cubic or inverted hexagonal H(II) aggregate structures. Together with the data on the transport and intercalation of the dimers into phospholipid liposomes mediated by the lipopolysaccharide-binding protein (LBP), our conformational concept of endotoxicity and cell activation can be applied to these non-LPS structures: endotoxically active compounds incorporate into membranes of immune cells and cause conformational changes at the site of signaling proteins such as Toll-like receptors or K(+)-channels due to their conical molecular shape.
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PMID:Structural polymorphism and endotoxic activity of synthetic phospholipid-like amphiphiles. 1504 11

Various chymotrypsin inhibitors occur in the hemolymph of silkworm larvae. Interaction of chymotrypsin inhibitor b1 (CI-b1) with Escherichia coli was examined from the viewpoint of action against invading bacteria. Injection of dead E. coli cells into larva reduced the CI-b1 content of the hemolymph, suggesting in vivo binding of CI-b1 to the outer membrane of the cell. Results from incubation of E. coli in cell-free hemolymph in the presence or absence of lipopolysaccharide indicated that CI-b1 is the only CI bound to E. coli and that it interacts with lipopolysaccharide. CI-b1 formed a complex with lipopolysaccharide in vitro; the value of the dissociation constant was relatively large. Inhibitory activity of CI-b1 changed insignificantly in mixture with lipopolysaccharide. CI-b1 affected the growth of E. coli but never worked lethally. CI-b1 is speculated to be a mediator that scavenges intruding bacteria rather than a direct anti-bacterial factor. This is the first report confirming that CI-b1 is a lipopolysaccharide binding protein.
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PMID:In vivo and in vitro interactions of the Bombyx mori chymotrypsin inhibitor b1 with Escherichia coli. 1511 11

Endotoxin-neutralizing protein (ENP) of the horseshoe crab is one of the most potent neutralizers of endotoxins [bacterial lipopolysaccharide (LPS)]. Here, we report on the interaction of LPS with recombinant ENP using a variety of physical and biological techniques. In biological assays (Limulus amebocyte lysate and tumour necrosis factor-alpha induction in human mononuclear cells), ENP causes a strong reduction of the immunostimulatory ability of LPS in a dose-dependent manner. Concomitantly, the accessible negative surface charges of LPS and lipid A (zeta potential) are neutralized and even converted into positive values. The gel to liquid crystalline phase transitions of LPS and lipid A shift to higher temperatures indicative of a rigidification of the acyl chains, however, the only slight enhancement of the transition enthalpy indicates that the hydrophobic moiety is not strongly disturbed. The aggregate structure of lipid A is converted from a cubic into a multilamellar phase upon ENP binding, whereas the secondary structure of ENP does not change due to the interaction with LPS. ENP contains a hydrophobic binding site to which the dye 1-anilino-8-sulfonic acid binds at a K(d) of 19 micro m, which is displaced by LPS. Because lipopolysaccharide-binding protein (LBP) is not able to bind to LPS when ENP and LPS are preincubated, tight binding of ENP to LPS can be deduced with a K(d) in the low nonomolar range. Importantly, ENP is able to incorporate by itself into target phospholipid liposomes, and is also able to mediate the intercalation of LPS into the liposomes thus acting as a transport protein in a manner similar to LBP. Thus, LPS-ENP complexes might enter target membranes of immunocompetent cells, but are not able to activate due to the ability of ENP to change LPS aggregates from an active into an inactive form.
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PMID:Biophysical characterization of the interaction of Limulus polyphemus endotoxin neutralizing protein with lipopolysaccharide. 1512 13

Genes encoding for receptors of the innate immune system are potential candidates for susceptibility to inflammatory bowel disease, e.g., mutations in the cytosolic receptor NOD2/CARD15 were associated with Crohn's disease. Herein, two mutations of the Toll-like receptor (TLR)-4 gene (Asp299Gly and Thr399Ile) resulting in impaired lipopolysaccharide signaling, the -159C/T promotor polymorphism of the CD14 gene, polymorphisms of the lipopolysaccharide binding protein gene and the bactericidal permeability increasing protein gene were evaluated in 102 patients with Crohn's disease, 98 patients with ulcerative colitis and 145 healthy controls. The allele and carrier frequencies for the Thr399Ile mutation in TLR4 gene were significantly increased in ulcerative colitis when compared to the controls (P = 0.014 and P = 0.018, respectively). None of the other five polymorphisms was associated with inflammatory bowel disease. In conclusion, a novel association between a functional polymorphism in TLR4 and ulcerative colitis is reported. This observation underscores the importance of impaired innate immunity in inflammatory bowel disease.
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PMID:Polymorphisms of the lipopolysaccharide-signaling complex in inflammatory bowel disease: association of a mutation in the Toll-like receptor 4 gene with ulcerative colitis. 1520 85

The aim of this study was to examine the inflammatory reaction occurring in the pleural space of patients suffering from primary spontaneous pneumothorax (PSP) using pleural lavage, which was performed in patients with PSP and in healthy control subjects (essential hyperhidrosis patients undergoing thoracoscopy for sympathicolysis treatment). Cellular and solute composition of lavage fluid, peripheral blood and parietal pleural biopsies were analysed. PSP lavage fluid showed an increase in all differentiated leucocytes, but most strikingly eosinophils and neutrophils. In the blood of patients with PSP, the total number of leucocytes and the absolute number of eosinophils, neutrophils and monocytes were also significantly increased. The time in which air was present in the pleural space was positively correlated with the increase of eosinophils in lavage fluid, parietal pleura and blood. Eosinophilic cationic protein was elevated after PSP and strongly correlated with the absolute number of lavage eosinophils. Chemo and cytokine analysis in lavage fluid showed differences in concentrations of interleukin (IL)-5, IL-6, IL-8, IL-12p40, tumour necrosis factor-alpha and RANTES, but not of eotaxin. Surprisingly, high levels of lipopolysaccharide binding protein were also measured. Primary spontaneous pnumothorax is associated with a substantial pleural inflammatory reaction. The authors hypothesise that mechanical stretch factors, lipopolysaccharide binding protein/lipopolysaccharide complexes or other environmental components trigger pleural inflammation after primary spontaneous pnumothorax.
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PMID:Characterisation of pleural inflammation occurring after primary spontaneous pneumothorax. 1521 4

Bacterial endotoxin (lipopolysaccharide, LPS) is responsible for the septic shock syndrome. As potential therapeutic agents cyclic cationic antimicrobial peptides of different length, based on the Limulus anti-lipopolysaccharide factor (LALF), were synthesized, and their interaction with LPS was characterized physico-chemically and related to results in biological assays. All peptides inhibited the LPS-induced cytokine production in human mononuclear cells and the Limulus amebocyte lysate in a concentration-dependent way, with the peptide comprising the complete LPS-binding loop of the LALF (cLALF22) being the most effective. The peptides were neither cytotoxic nor hemolytic, except a slight effect of cLALF22. The peptides were able to displace Ca(2+) cations from a LPS monolayer, with cLALF22 being again most effective in accordance with results from isothermal titration calorimetry, in which saturation of binding was observed at an equimolar [cLALF22]:[LPS] ratio, and at a ratio 2-2.5 for the other peptides. For cLALF22, zeta (xi) potential experiments exhibited a complete compensation of the negative charges of LPS, whereas for the other peptides a residual negative potential of -20 to -40mV was found. X-ray diffraction experiments showed that the mixed unilamellar/cubic inverted aggregate structure of the lipid A part of LPS was converted into a multilamellar one. The gel to liquid crystalline phase transition of the acyl chains of LPS was changed upon cLALF22 binding, leading to a clear fluidization, which was not observed or only to a lesser degree for the other peptides. The affinity of the peptides for LPS led to a reduced binding of lipopolysaccharide-binding protein (LBP) to target membranes and hence to an inhibition of cytokine induction in human mononuclear cells.
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PMID:Cyclic antimicrobial peptides based on Limulus anti-lipopolysaccharide factor for neutralization of lipopolysaccharide. 1534 19


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