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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With a 2.9-mM concentration of unlabelled bovine serum albumin (BSA), the FITC-albumin transport (2 mg included) across the omental monolayer (0.48 +/- 0.16 mg/ml/30 min) was found to be significantly reduced as compared with the interstitial BSA concentration (290 microM) as it is the case, e.g., in peritonitis (0.79 +/- 0.09 mg/ml/30 min). Adding 10 micrograms lipopolysaccharide (LPS)/ml from Escherichia coli, serotype 0128:B12, we did not see any differences from the control. Cultured mesothelial cells took up double the amount of FITC-albumin (4.2 +/- 0.13 micrograms/10(5) cells/30 min) and in the presence of LPS the uptake of FITC-albumin was reduced to half the control (2.15 +/- 0.47 micrograms/10(5) cells/30 min). The results reveal the active participation of the mesothelium because high concentrations of BSA reduced exocytosis and stimulated endocytosis. Applying 10 micrograms/ml of LPS turned out to influence endocytosis and to reduce it at a high BSA concentration.
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PMID:Endotoxin effects on transmesothelial transport and intracellular uptake of albumin. 180 34

To further examine the effects of purified Haemophilus influenzae type b lipopolysaccharide (LPS) on blood-brain barrier permeability, we have developed an in vitro model of the BBB. Microvascular endothelial cells were isolated from rat cerebral cortices by enzymatic digestion, dextran centrifugation, and separation on percoll gradients. The cells were determined to be endothelial in origin by positive fluorescent staining for Factor VIII-related antigen and the ability to take up acetylated low density lipoproteins, and their cerebral origin by the formation of junctional complexes in vitro. Cells were seeded onto semipermeable polycarbonate filters and permeability assessed by measuring traversal of radioactive albumin across the monolayer. Treatment of the cells with LPS at concentrations of 1.0 microgram/ml and 0.1 microgram/ml for 4 h led to statistically significant increases in albumin permeability of 4.6% (P = 0.001) and 5.6% (P less than 0.001), respectively, without evidence of cell death as assessed by release of lactate dehydrogenase into the media. These results indicate that LPS significantly increases albumin permeability across a monolayer of cerebral microvascular endothelial cells in the absence of host inflammatory cells. Future studies on the effects of LPS on intracellular regulation will determine the mechanisms responsible for these alterations.
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PMID:Blood-brain barrier alterations in bacterial meningitis: development of an in vitro model and observations on the effects of lipopolysaccharide. 182 2

Bacterial lipopolysaccharide (LPS) and an N-formyl peptide, N-formyl-neoleucyl-leucyl-phenylalanine (FNLP), synergistically promote lung injury in rats as measured by 125I-labeled albumin flux. Concomitantly, neutrophils are sequestered in the lung. We hypothesized that LPS-FNLP-induced lung injury is mediated both by neutrophil-dependent and -independent mechanisms. Rats were depleted of circulating and marginating neutrophils with vinblastine. LPS-FNLP-induced lung protein leak was partially decreased in these neutrophil-depleted animals, although a component of lung injury remained. We hypothesized that LPS-FNLP-induced lung injury was also mediated by xanthine oxidase (XO). Rats were fed a tungsten-enriched diet that inactivates molybdenum-dependent oxidase systems. LPS-FNLP-induced lung leak was partially decreased in these animals as well. When tungsten-fed rats were also neutrophil depleted with vinblastine, no increase in 125I-albumin flux was observed in response to LPS-FNLP. In parallel experiments, lungs from vinblastine-pretreated rats were isolated and perfused. FNLP infusion into the LPS-primed, crystalloid-perfused lungs caused increased 125I-albumin flux, which was prevented by oxidase inhibition. We conclude that LPS-FNLP-induced lung injury is both neutrophil mediated and neutrophil independent. The nonneutrophil component of the LPS-FNLP-induced lung injury appears to be pulmonary XO derived and dependent.
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PMID:FNLP injures endotoxin-primed rat lung by neutrophil-dependent and -independent mechanisms. 184 3

Injury to the blood brain barrier (BBB) is a fundamental sequela of bacterial meningitis, yet the precise mechanism facilitating exudation of albumin across the endothelium of the cerebral microvasculature remains conjectural. After intracisternal inoculation of Escherichia coli (0111:B4) lipopolysaccharide in rats to elicit a reversible meningitis and BBB injury, we utilized in situ tracer perfusion and immunolabeling procedures to identify by transmission electron microscopy the precise topography and microvascular exit pathway(s) of bovine serum albumin (BSA). Results revealed that during meningitis there was: (a) an inducible increase in immunodetectable monomeric BSA binding to the luminal membrane of all microvascular segments in the pia-arachnoid and superficial brain cortex; (b) similar uptake of both colloidal Au-BSA (as well as monomeric BSA) by plasmalemmal vesicles but no detectable transcytosis to the abluminal side; and (c) predominant exit of both perfused Au-BSA and immunodetectable monomeric BSA through open intercellular junctions of venules in the pia-arachnoid. This was corroborated in separate experiments documenting focal pial venular leaks of in situ perfused 0.01% colloidal carbon black during experimental meningitis. These results provide precise localization of BBB injury in meningitis to meningeal venules, confirm a paracellular exit pathway of albumin via open intercellular junctions, and suggest an injury mechanism amenable to specific therapeutic intervention.
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PMID:Ultrastructural localization of albumin transport across the cerebral microvasculature during experimental meningitis in the rat. 187 66

The effects of polyclonal antibodies to mouse serum components on the primary humoral immune response of mice in vivo were studied. It was observed that rabbit IgG to complement component C3 and albumin and mouse IgG to C5, but also heat-aggregated non-immune rabbit IgG, enhanced the agglutinating antibody response to sheep erythrocytes (SRBC). Since the increase in response was only observed when antigen and antibodies were administered via the same route (i.p.), immunological adjuvant activity was implicated. Ineffectiveness of anti-C5 IgG in C5-deficient mice indicated that the antibody-induced adjuvant activity is mediated by in vivo formed immune complexes (IC). The adjuvant activity of IC was reduced by selective C3-depletion of animals, pointing to a requirement of C3. The effect of variations in other parameters was studied with anti-C3 and anti-C5 IgG as immunoadjuvant. The immunostimulatory effect was most pronounced when the antibodies were administered simultaneously with or shortly before antigen. Treatment of animals with antibodies one or two days before antigen, however, resulted in a suppression of the response. The response to thymus-independent antigens was not enhanced by anti-C3 nor by anti-C5 IgG. Optimal adjuvant activity of anti-C3 IgG was observed at low antigen doses. Nude mice were insensitive to the immunopotentiating effect of anti-C3 and so was the F1 progeny of BALB/c male and CBA/N female mice expressing a B-cell maturation defect. C5 deficiency and lipopolysaccharide (LPS) non-responsiveness did not affect the adjuvant activity of in vivo formed C3-anti-C3 IC.
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PMID:C3- and T-cell-dependent adjuvant activity of in vivo formed immune complexes. 187 75

Non-ionic block copolymers and lipopolysaccharides are both effective immunological adjuvants which are thought to act via distinct mechanisms. We hypothesized that they might produce synergistic effects when used together. We prepared a series of lipopolysaccharide (LPS) preparations ranging from the smallest precursor, lipid X through complete LPS with O-polysaccharide chains. Three preparations with reduced toxicity, monophosphoryl lipid A, partially hydrolysed Ra-LPS and LPS of Rhodopseudomonas sphaeroides were also utilized. All LPS preparations except the smallest were effective adjuvants for inducing early antibody responses to trinitrophenyl-conjugated hen egg albumin (TNP-HEA) when injected in squalane-in-water emulsions with copolymer L141. Only the larger LPS preparations induced sustained antibody responses. By itself, emulsions of copolymer L141 induced a predominant IgG1 antibody isotype response with lesser amounts of IgG2a and IgG2b. Surprisingly, all of the LPS preparations tested increased the proportion of IgG2 isotypes even though some had little effect on overall titres. The detoxified Ra-LPS (Ra-detox) was the most effective preparation for both increasing antibody titres and inducing the desirable IgG2a and IgG2b isotypes. These results demonstrate that the combination of LPS and block polymer adjuvants can produce synergistic effects without unacceptable toxicities.
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PMID:Adjuvant activity of non-ionic block copolymers. V. Modulation of antibody isotype by lipopolysaccharides, lipid A and precursors. 205 68

We have previously shown that albumin-complexed stearic acid (18:0) inhibited in vitro primary anti-TNP plaque-forming cell (PFC) responses to trinitrophenyl keyhole limpet hemocyanin (TNP-KLH), but did not affect primary PFC responses to trinitrophenyl lipopolysaccharide (TNP-LPS). The present studies were done to identify the cellular target of fatty acid inhibition. The addition of 18:0 at the initiation of antibody cultures exerted a dose-dependent inhibitory effect on subsequent PFC responses to TNP-KLH, and removal of the fatty acid after 20 h did not reverse its inhibitory effect. Preincubation of isolated T-cells with TNP-KLH and 18:0 resulted in a similar inhibition of subsequent PFC responses, but a preincubation of isolated B-cells had no effect. The addition of 18:0 to the culture system in vitro led to a marked reduction in the level of IL-2 detectable in culture supernatants, and PFC responses could be restored by providing exogenous mouse recombinant IL-2. The addition of antigen-primed T-helper cells to antibody cultures partially abrogated the inhibition by 150 microM 18:0, apparently due to their greater production of IL-2. Lastly, following overnight incubation of unfractionated splenic lymphocytes in the presence of TNP-KLH and [1-14C]-18:0, B-cells were shown to contain nearly 5-fold more radiolabeled oleic acid (18:1) than T-cells. Collectively, these findings implicate T-helper cells as the principle target of 18:0-inhibition of primary antibody responses in vitro, possibly as a result of the inability of T-helper cells to avoid an over accumulation of stearic acid in their membrane phospholipids.
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PMID:Identification of T-helper cells as the target of stearic acid-inhibition in primary antibody responses in vitro. 214 47

Induction of C-reactive protein (CRP) by conditioned medium from lipopolysaccharide-stimulated human monocytes in two human hepatoma-cell lines, Hep 3B and NPLC/PRF/5, was potentiated 3-6-fold by the methylxanthine caffeine. The induction observed in the presence of conditioned medium plus caffeine was as much as 180-fold, comparable with that seen after many stimuli in vivo. This potentiation was accompanied by an increase in the levels of CRP mRNA. By contrast, no potentiating effect on CRP induction by conditioned medium was found when we tested theophylline, forskolin, 8-bromo cyclic AMP or two Ca2+ ionophores, namely ionomycin and A23187. None of the above compounds, including caffeine, when tested alone, had any detectable effect on the synthesis and secretion of CRP. Our previous study [Ganapathi, May, Schultz, Brabenec, Weinstein, Sehgal & Kushner (1988) Biochem. Biophys. Res. Commun. 157, 271-277], employing defined cytokines, had shown that induction of CRP in Hep 3B cells requires IL(interleukin)-6 plus IL-1, whereas, in the NPLC/PRF/5 cell line, IL-6 alone is effective. Caffeine similarly potentiated induction of CRP by these defined cytokine signals in these two cell lines. Changes in synthesis of other acute-phase proteins, including serum amyloid A (SAA), alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin and albumin, induced by conditioned medium or, in some cases, by IL-6 and/or IL-1 alpha, were only minimally affected by caffeine. Thus these results indicate that the mechanism by which caffeine potentiates CRP induction by cytokines appears to be independent of increases in intracellular concentrations of the two second messengers, cyclic AMP and Ca2+; the precise nature of this mechanism is unclear at the present time. Our results also indicate that the intracellular mechanisms by which cytokines regulate synthesis of CRP may differ from those regulating synthesis of some other acute-phase proteins. The differential response of CRP and SAA to caffeine is of particular interest, since induction of both of these two major acute-phase proteins can be accomplished by identical extracellular signals.
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PMID:Induction of C-reactive protein by cytokines in human hepatoma cell lines is potentiated by caffeine. 216 98

Media conditioned by an interleukin 3 (IL-3)-producing T-cell line, STIL-3, as well as recombinant mouse IL-3 showed granulocyte/macrophage (GM) colony-stimulating activity in the semi-solid culture medium containing horse serum (HS) or bovine serum, but the activity was not apparent when fetal calf serum (FCS) was used. No such serum-dependency of GM colony formation was observed when abdominal wall conditioned medium or L-cell conditioned medium containing GM colony-stimulating factor was used. Although the levels of albumin and total protein were lower in FCS than HS, increase of FCS concentration did not affect the GM colony-stimulating activity of IL-3. Addition of bovine serum albumin (BSA) preparation to FCS, however, increased the number of GM colonies to the same level as that observed with HS. The levels of bacterial lipopolysaccharide (LPS) in sera and BSA and the effect on the bone marrow cells from LPS-nonresponsive C3H/HeJ mice indicated that the observed effect of BSA was not due to the contaminating LPS. The activity of BSA was not substituted by IL-1, IL-2, IL-4, IFN-gamma, TNF, NGF or erythropoietin. The present study suggests the presence in BSA of co-factor(s) of IL-3 in stimulating GM colony formation.
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PMID:Presence of an activity indispensable for the granulocyte/macrophage colony-stimulating activity of interleukin 3 in bovine serum albumin. 217 34

Multiple extrapulmonary organ system failures increase mortality, permeability edema, and alveolar inflammation during gram-negative sepsis because of abnormal regulation of host inflammatory responses. We tested the hypothesis that acute hepatocytic injury induced by the selective hepatotoxin, D-galactosamine (GalN), augments mortality and amplifies pulmonary microvascular permeability to albumin and neutrophilic influx after administering Escherichia coli lipopolysaccharide (LPS) 24 h later by impairing the metabolism of endogenously synthesized products of arachidonic acid. We determined the lung extravascular leak of 125I-human serum albumin measured at multiple time points after LPS and enumerated polymorphonuclear leukocytes (PMNs) in bronchoalveolar lavage fluid (BALF). Because the liver is important in prostaglandin (PG) and leukotriene (LT) metabolism, we measured plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2 (TxB2) in addition to paired plasma BALF concentrations of LTB4 and BALF LTC4 60 min and 24 h after LPS. We further assessed the protective effects of a single 20-mg/kg injection given intraperitoneally (i.p.) of the LTA4 synthetase inhibitor, diethylcarbamazine (DEC). After 400 mg/kg GalN, LPS at 2.5 or 1.25 mg/kg i.p. increased mortality (p less than 0.001), albumin leak 60 and 90 min after LPS (p less than 0.05), plasma 6-keto-PGF1 alpha, TxB2, and LTB4 levels and BALF LTC4 within 60 min (p less than 0.05). LTB4 and LTC4 levels in BALF 24 h later were similarly increased (p less than 0.05) as were bronchoalveolar PMNs (p less than 0.001). DEC improved mortality and albumin leak (p less than 0.001), reduced lung influx of PMNs and peripheral leukocytosis (p less than 0.05), attenuated plasma LTB4 and BALF LTC4 levels 60 min after LPS (p less than 0.05), and decreased BALF LTB4 and LTC4 at 24 h (p less than 0.05), but was associated with higher plasma 6-keto-PGF1 alpha and TxB2 values at 60 min. Changes in eicosanoid levels and modulation of responses by DEC in this model suggest that impaired metabolism of endogenously synthesized leukotriences by the damaged liver underlies these phenomena. We conclude that this mechanism may enhance septic lung injury during acute liver dysfunction.
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PMID:Effects of D-galactosamine-induced acute liver injury on mortality and pulmonary responses to Escherichia coli lipopolysaccharide. Modulation by arachidonic acid metabolites. 218 85


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