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)

A recombinant (r) NH2-terminal fragment of bactericidal/permeability-increasing protein, rBPI23, was shown to inhibit murine macrophage nitric oxide (NO) production elicited by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). Normal mouse plasma amplified NO synthesis (measured as NO2- release) at LPS concentrations of 1-10 ng/mL, and antibody to the plasma LPS-binding protein (LBP) partially inhibited NO2- release in the presence of normal mouse plasma. rBPI23 (1 microgram/mL) effectively inhibited LPS-dependent NO2- release in the presence or absence of normal mouse plasma. Fifty percent inhibition of IFN-gamma/LPS-elicited NO2- production or of binding of fluoresceinated LPS was obtained with approximately 0.2 microgram/mL rBPI23. These results provide a basis for studies of rBPI23 effects on NO synthase activity in murine models of gram-negative sepsis.
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PMID:Bactericidal/permeability-increasing protein inhibits induction of macrophage nitric oxide production by lipopolysaccharide. 827 72

The bactericidal/permeability-increasing protein (BPI) inhibits the lipopolysaccharide (LPS)-mediated activation of monocytes. Due to its inhibitory activity for various LPS, BPI has therapeutic potential in endotoxic shock. To be efficient in vivo, BPI should overcome the action of LPS-binding protein (LBP), a serum molecule that increases the expression of LPS-inducible genes via CD14 of monocytes, rBPI23, a recombinant fragment of BPI, prevented in a dose-dependent manner the binding and the internalization of LPS mediated by LBP. Consequently, rBPI23 also inhibited LPS-induced tumor necrosis factor (TNF alpha) synthesis from monocytes. LPS- and LBP-mediated activation of monocytes was totally inhibited when LPS was preincubated with rBPI23. Adding rBPI23 at the same time as LBP resulted in an important but partial inhibition of TNF alpha release, but this inhibition vanished with delaying the time of addition of rBPI23. These studies suggest that the inhibitory activity of BPI is related to its ability to compete with LBP for LPS.
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PMID:Competition between bactericidal/permeability-increasing protein and lipopolysaccharide-binding protein for lipopolysaccharide binding to monocytes. 850 24

Bactericidal/permeability-increasing protein [BPI] is a cationic antimicrobial protein from neutrophils that specifically binds to the surfaces of Gram-negative bacteria via the lipid A component of lipopolysaccharide. To obtain information about the responses of Salmonella typhimurium to cell-surface damage by BPI, two-dimensional gel electrophoresis and N-terminal microsequencing were used to identify proteins that were induced or repressed following BPI treatment. The majority of the affected proteins are involved in central metabolic processes. Upon addition of BPI, the beta-subunit of the F1 portion of Escherichia coli ATP synthase was repressed threefold whereas six proteins were induced up to 11-fold. Three of the latter were identified as lipoamide dehydrogenase, enoyl-acyl carrier protein reductase, and the heat-shock protein HtpG. Additionally, a novel protein, BipA, was identified that is induced over sevenfold by BPI; sequence analysis suggests that it belongs to the GTPase superfamily and interacts with ribosomes. A conserved direct-repeat motif is present in the regulatory regions of several BPI-inducible genes, including the bipA gene. Only one of the BPI-responsive proteins was induced when cells were treated with polymyxin B, which also binds to lipid A. We therefore conclude that BPI and polymyxin B affect different global regulatory networks in S. typhimurium even though they bind with high affinity to the same cell-surface component.
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PMID:Salmonella typhimurium responses to a bactericidal protein from human neutrophils. 855 71

This study was performed to clarify the mechanisms underlying post-resection changes in liver cell proliferation and metabolism. To assess the role of gut-derived endotoxaemia and endogenous cytokines in these changes, the effects of peri-operative treatment with either the lipopolysaccharide-neutralizing bactericidal/permeability-increasing protein or interleukin-1 receptor antagonist were investigated at 24 h after two-thirds hepatectomy in rats. Peri-operative treatment with either agent caused enhanced expression of proliferating cell nuclear antigen (PCNA) and reduced lipid accumulation. Activity of the hexose monophosphate shunt was significantly decreased after partial hepatectomy and restored by interleukin-1 receptor antagonist only. After partial hepatectomy, bile canalicular alkaline phosphatase activity was significantly increased in pericentral zones and redistributed to both bile canalicular and sinusoidal membranes of hepatocytes. These effects were not significantly influenced by either treatment. It is concluded that endotoxin restricts liver cell proliferation and leads to lipid accumulation following partial hepatectomy, and that interleukin-1 is a principal mediator in these processes. Furthermore, interleukin-1 mediates a repression of the pentose phosphate pathway. These changes may be of significance with respect to liver function, at least in the early phase after partial hepatectomy.
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PMID:Endotoxin- and cytokine-mediated effects on liver cell proliferation and lipid metabolism after partial hepatectomy: a study with recombinant N-terminal bactericidal/permeability-increasing protein and interleukin-1 receptor antagonist. 869 33

rBPI23 is a biologically active, recombinant N-terminal fragment of human bactericidal/permeability-increasing protein (BPI). While rBPI23 is readily purified from culture supernatants of Chinese hamster ovary (CHO)-K1 transfectants, it is heterogeneous, consisting of monomer and disulfide-linked dimer, characteristics due presumably to the presence of three cysteines within the molecule. We have examined the role of these cysteines in rBPI23 expression, function, and dimer formation by mutating their codons to alanine (C132A), serine (C135S), or alanine (C175A) and expressing analogues of N-terminal fragments ("variants") lacking one, two, or all three cysteines in permanently transfected CHO-K1 cells. We also expressed a variant in which serine 18 was changed to cysteine (S18C), as found in both bovine and rabbit BPI. The C132A variant was readily secreted and purified as a homogeneous, stable monomeric protein species. The C135S and S18C variants were produced as mixtures of monomer and dimer; the C135S variant was poorly secreted, difficult to purify, and unstable on storage. In contrast, the C175A variant and those lacking any two or all three cysteines were expressed but not secreted. Purified rBPI23 and the C132A and S18C variants had comparable bactericidal and lipopolysaccharide (LPS) binding activities and were similarly effective at neutralizing LPS-induced tumor necrosis factor synthesis by THP-1 cells; the purified C135S variant lacked all activities. From these studies with CHO-K1 transfectants, we conclude that (i) cysteines 135 and 175 are both necessary for efficient secretion of a biologically active N-terminal BPI fragment, presumably through the formation of a disulfide bond, (ii) cysteine 132 is responsible for dimer formation, and (iii) only the C132A modification yields a stable, biologically active, N-terminal BPI fragment (designated rBPI21) that is free of dimeric species.
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PMID:Expression and characterization of cysteine-modified variants of an amino-terminal fragment of bactericidal/permeability-increasing protein. 881 32

In this study, the release of bactericidal/permeability-increasing protein (BPI), which is stored in polymorphonuclear leukocytes (PMNL), was analyzed in a whole blood ex vivo system. Of the microbial products tested, lipopolysaccharide (LPS) most potently induced BPI release; FMLP, serum-treated zymosan (STZ), and lipoteichoic acid (LTA) also induced BPI release. In addition, the inflammatory mediator tumor necrosis factor (TNF)-alpha potently activated PMNL in whole blood, via TNF receptor p55, to release BPI, whereas interleukin (IL)-1, IL-8, platelet activating factor, and C5a were poor inducers of BPI release. STZ and phorbol myristate acetate, but not LPS, FMLP, or LTA, stimulated isolated PMNL to release BPI. BPI was released in comparable magnitude with the azurophilic granule protein elastase. Furthermore, both proteins were released with similar kinetics, which started within 30 min after onset of stimulation and lasted 1-4 h.
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PMID:Bactericidal/permeability-increasing protein release in whole blood ex vivo: strong induction by lipopolysaccharide and tumor necrosis factor-alpha. 898 3

The physiological response to endotoxin (lipopolysaccharide (LPS)) can be regulated by two closely related LPS-binding proteins, LPS-binding protein (LBP), which potentiates LPS' inflammatory activity via interaction with the monocytic antigen CD14, and bactericidal/permeability-increasing protein (BPI), which neutralizes LPS. Both proteins bind LPS with high affinity sites in their N-terminal domains, whereas interaction between LBP and CD14 is dependent upon the LBP C-terminal domain. We have created fusions of the N- and C-terminal domains from each protein and compared the functional activities and pharmacokinetics of these fusions, the individual N-terminal domains, and the parent proteins. The N-terminal domains of BPI and LBP bound lipid A with their characteristic apparent affinity constants, regardless of the C-terminal fusion partner. In addition, the C-terminal domain of LBP allowed transfer of LPS to CD14 in conjunction with either N-terminal LPS binding domain. Proteins containing a BPI N-terminal domain had greater heparin binding capacities in vitro and were cleared more rapidly from the plasma of whole animals. Taken together, these data better define how closely related proteins such as BPI and LBP can have opposing effects on the body's response to LPS.
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PMID:Biochemical characterization of recombinant fusions of lipopolysaccharide binding protein and bactericidal/permeability-increasing protein. Implications in biological activity. 899 16

We used rough lipopolysaccharide (ReLPS) to construct a fluorescein-labeled LPS (FITC-LPS) with a very high labeling efficiency that bound to isolated human monocytes in a CD14-dependent fashion and that in this respect behaved indistinctively from native LPS. The CD14-dependent binding could be inhibited either by a 1,000-fold excess of unlabeled LPS or by polymyxin B, bactericidal/permeability-increasing protein, cationic protein 18, or soluble CD14. Although this FITC-LPS preparation no longer possessed the ability to prime neutrophils for the production of reactive oxygen species or to stimulate human monocytes to produce tumor necrosis factor, activation of the Limulus amoebocyte lysate cascade was comparable to activation by native LPS. Binding to monocytes was enhanced by human pooled serum (HPS) or LPS-binding protein (LBP) for LPS concentrations up to 100 ng/ml and was completely CD14 dependent. For LPS concentrations exceeding 100 ng/ml, binding was still partially CD14 dependent, but not HPS or LBP dependent. CD14-dependent association of LPS with monocytes was shown to be totally saturable. In conclusion, we found an HPS- or LBP-dependent binding of FITC-LPS to monocytes that was CD14 dependent at up to 100 ng of LPS per ml, and saturation of binding was shown.
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PMID:Saturable CD14-dependent binding of fluorescein-labeled lipopolysaccharide to human monocytes. 916 63

We have investigated the mechanisms of interaction of the recombinant N-terminal portion of bactericidal/permeability-increasing protein, rBPI21, with lipopolysaccharide (LPS) isolated from enterobacterial deep rough mutant strains. Experimentally, the ability of rBPI21 to form monolayers at the air/water interface and its action on lipid monolayers were analyzed. We have further studied the interaction of rBPI21 with aggregates from phospholipids and Re mutant LPS by infrared and resonance energy transfer spectroscopy and laser Doppler velocimetry. From monolayer experiments, the molecular area of a single rBPI21 molecule was estimated to be about 12 nm2. At lateral pressures of </=25 mN/m, rBPI21 incorporated into monolayers from negatively charged LPS and phosphatidylglycerol (PG) but not into those from neutral phosphatidylcholine. rBPI21 incorporated not only into monolayers but also into liposomes made from or containing negatively charged phospholipids, reducing the absolute value of the zeta-potential of LPS and PG aggregates. Furthermore, due to intercalation, rBPI21 caused the rigidification of the acyl chains of lipids in the gel as well as in the fluid phase and significantly immobilized their phosphate groups. High concentrations of Mg2+ ions were found to have a protective effect against the action of rBPI21. On the basis of these results, the biophysical characteristics of rBPI21 are discussed and a model is proposed as to how the rBPI21-induced influence on lipid monolayers and bilayers could explain rBPI21-mediated effects on the bacterial membrane.
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PMID:Mechanisms of action of the bactericidal/permeability-increasing protein BPI on endotoxin and phospholipid monolayers and aggregates. 925 29

The mechanisms of interaction of the recombinant N-terminal portion of bactericidal/permeability-increasing protein, rBPI21, with various planar asymmetric and symmetric bilayer membranes, including the lipid matrix of the outer membrane of Gram-negative bacteria, were investigated via electrical measurements. For the lipopolysaccharide (LPS) leaflet of the outer membrane, isolated deep rough mutant LPS of Escherichia coli strain F515 (F515 LPS) and Proteus mirabilis strain R45 (R45 LPS) were used. The addition of rBPI21 to the LPS side of asymmetric LPS/phospholipid membranes, as well as to black lipid membranes made from dioleoylphosphatidylglycerol (DOPG), led to membrane rupture. The innermembrane potential difference resulted in a slight increase from 0 to 5 mV for symmetric DOPG membranes but changed for asymmetric F515 LPS/PL membranes from -36 to +8 mV and for R45 LPS/PL membranes from -37 to -5 mV following the addition of rBPI21. In all cases, the addition of rBPI21 led to an increase in membrane current. The effect of rBPI21 on the innermembrane potential difference of LPS/PL membranes was significantly reduced in the presence of 40 mM MgCl2 (shift from -36 to -31 mV for F515 LPS). On the basis of these results and from our studies on the interaction of rBPI21 with lipid monolayers and aggregates [Wiese, A., et al. (1997) Biochemistry 36, 10301-10310], a model is discussed explaining how the observed membrane rupture, increase of membrane current, and change of transmembrane potential as induced by rBPI21 may contribute to bacterial dysfunction.
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PMID:Mechanisms of action of bactericidal/permeability-increasing protein BPI on reconstituted outer membranes of gram-negative bacteria. 925 30


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