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)

The purpose of this study was to determine if Pasteurella haemolytica can directly injure bovine pulmonary endothelial cells (EC) and if neutrophils have a beneficial or detrimental role in bacterium-EC interaction. Various combinations of live P. haemolytica, heat-killed P. haemolytica, anti-P. haemolytica immune serum, polymyxin B, and bovine neutrophils were added to confluent monolayers of bovine EC. Monitoring included determination of 51Cr release from EC, phase microscopy, and transmission electron microscopy. Although toxic changes were not evident at 5 h postinoculation, both live and heat-killed P. haemolytica produced extensive EC damage by 22 h postinoculation. Damage by live P. haemolytica was prevented only when both neutrophils and immune serum were used. Polymyxin B effectively prevented the toxic effect of heat-killed P. haemolytica, suggesting that lipopolysaccharide was the major toxic factor. Morphological studies showed close apposition of P. haemolytica to EC membranes, neutrophil activation, and adherence to EC but no evidence of neutrophil-associated EC membrane damage. These studies demonstrate that neutrophils and immune serum in combination are effective in preventing EC damage mediated by live P. haemolytica.
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PMID:Protective role of bovine neutrophils in Pasteurella haemolytica-mediated endothelial cell damage. 193 16

Exposure to lipopolysaccharide (LPS) primes polymorphonuclear leucocytes (PMNL) for enhanced release of oxygen metabolites after subsequent stimulation. The metabolic response of human PMNL primed with LPS and stimulated with formyl-methionyl-leucyl-phenylalanine (FMLP) was measured by chemiluminescence (CL) as a parameter for endotoxic activity. Polymyxin B (PMB) and monoclonal antibodies (MAbs) with specificity for lipid A were tested for inhibition of the priming effect of Re LPS of Salmonella minnesota R595, Rc LPS of Escherichia coli J5 and smooth LPS of E. coli O111. The CL response of PMNL primed with Re LPS or Rc LPS was higher than that of PMNL primed with smooth LPS. Pre-incubation of rough or smooth LPS with PMB caused dose-dependent inhibition of priming of PMNL. Two IgM MAbs, 8-2 and 26-20, which recognise different epitopes on the hydrophobic part of lipid A, also completely prevented priming of PMNL by either rough or smooth LPS. The dose-dependent inhibitory effect of both MAbs was similar to the inhibition by PMB. These results indicate that the binding of MAbs to the hydrophobic part of lipid A is important in blocking lipid A-mediated effects.
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PMID:Inhibition by lipid A-specific monoclonal antibodies of priming of human polymorphonuclear leucocytes by endotoxin. 202 18

Polymyxin B (PB) completely or at least significantly inhibited the capacity of Shigella dysenteriae 1 cells and the lipopolysaccharide (LPS) and lipid A (LA) subunits of several bacterial endotoxins to induce interferon (IFN) in rabbits. Animals injected with LPS inactivated by PB to the point of not inducing detectable IFN levels did not develop hyporesponsiveness to secondary IFN induction by a homologous inducer. It was concluded that PB inhibits the IFN-inducing capacity of endotoxin and its subunits as a consequence of binding to the LA-moiety of LPS. The results confirmed the exclusive role of LA as the only IFN-inducing component of Gram-negative bacterial endotoxin.
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PMID:Inactivation by polymyxin B of the endotoxin-mediated interferon production in the rabbit. 241 51

Polymyxin B (PmB) blocks many of the toxic effects of lipopolysaccharide by mechanisms that are not yet understood. The production of tumor necrosis factor-alpha (TNF-alpha) by isolated rat alveolar macrophages in response to lipopolysaccharide and macrophage-activating factor was blocked by PmB at concentrations of 100, 10, and 1 micrograms/ml. Gentamicin enhanced rather than inhibited TNF production at the 100-micrograms/ml concentrations and had no effect at low concentration. Similar inhibitory effects were induced by PmB in an in vivo model in which rat macrophage TNF production was stimulated by intratracheally injected lipopolysaccharide. Because many of the effects of lipopolysaccharide are mediated by TNF, this inhibition provides a mechanism to explain the protection afforded by PmB against lipopolysaccharide-induced toxicity.
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PMID:Polymyxin B prevents lipopolysaccharide-induced release of tumor necrosis factor-alpha from alveolar macrophages. 254 12

Polymyxin B, a relatively toxic antibiotic, has potent endotoxin-neutralizing properties that may be beneficial as adjunctive therapy in gram-negative sepsis. Polymyxin B nonapeptide (deacylated polymyxin B) is devoid of antibiotic activity but retains the capacity to disorganize the outer membrane of gram-negative bacteria. To evaluate the potential therapeutic usefulness of this derivative, we produced purified polymyxin B nonapeptide, tested its in vivo toxicity in animals, and evaluated its in vitro antiendotoxin activity. Effectiveness as an antiendotoxin agent was assessed by examining the ability of polymyxin B nonapeptide to block the enhanced release of toxic oxygen radicals induced by lipopolysaccharide in human neutrophils (priming). In vivo, at doses of 1.5 and 3.0 mg/kg, polymyxin B nonapeptide did not exhibit the neuromuscular blocking, neurotoxic, or nephrotoxic effects that were observed with polymyxin B sulfate. Both polymyxin B and polymyxin B nonapeptide inhibited lipopolysaccharide-induced neutrophil priming in a concentration-dependent manner, but the parent compound, polymyxin B, was 63 times more effective on a weight basis. The inhibitory activity of both compounds, however, diminished rapidly when they were added after the start of the lipopolysaccharide-neutrophil incubation. We conclude that polymyxin B nonapeptide is less toxic than polymyxin B and, at the doses tested, lacks the neurotoxicity and nephrotoxicity of the parent compound. Polymyxin B nonapeptide retains the antiendotoxin activity of polymyxin B but is much less potent. The findings suggest that these compounds block an early step in the neutrophil priming process, possibly lipopolysaccharide attachment to or insertion into the neutrophil membrane.
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PMID:Purification, toxicity, and antiendotoxin activity of polymyxin B nonapeptide. 255 95

Mutants of Escherichia coli susceptible to vancomycin were isolated after mutagenesis with nitrosoguanidine. One such mutant was studied extensively. Multiple regression analysis of the relationship between physical properties of 20 glycopeptides and their in vitro activities against the vancomycin-susceptible mutant revealed a significant correlation with molecular mass (P = 0.007). pI, hydrophobicity, and affinity of the glycopeptide for the pentapeptide target were not as important for activity. This suggested that a block of access of the antibiotic to its target could be the major factor determining activity. Outer membrane proteins of the vancomycin-susceptible mutant, resistant parent, and revertant strains appeared normal. The mutant exhibited increased susceptibility to both erythromycin and fusidic acid which was lost in single-step revertants to vancomycin resistance. Polymyxin B nonapeptide was synergistic with erythromycin and fusidic acid against the parent and revertant but not against the susceptible mutant. Analysis of the susceptibilities of control strains of E. coli and Salmonella typhimurium with known defects in lipopolysaccharide (LPS) synthesis revealed that core LPS mutants (Re chemotype) were phenotypically similar to the E. coli mutant under study. However, the LPS core of the mutant migrated slightly less rapidly on sodium dodecyl sulfate-polyacrylamide gel electrophoresis than wild-type or revertant core LPS and did not resemble Re chemotype LPS core obtained from Salmonella rfaC and rfaD mutants. These data suggest that defects in LPS core structure other than loss of heptose moieties may also be important in loss of resistance to large, hydrophilic molecules such as glycopeptides.
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PMID:Escherichia coli susceptible to glycopeptide antibiotics. 265 29

Haemophilus influenzae type b (Hib) lipopolysaccharide (LPS) may be present in the cerebrospinal fluid largely as part of outer membrane vesicles (OMV), which could possibly alter its activity. Similar to inoculation of purified Hib LPS, intracisternal inoculation of Hib OMV into adult rats resulted in dose- and time-dependent increases in blood-brain barrier permeability. Polymyxin B, but not an oligosaccharide-specific monoclonal antibody, significantly inhibited the activity of Hib OMV. No change in blood-brain barrier permeability occurred in leukopenic rats inoculated with Hib OMV. Hib OMV was as active as purified Hib LPS on a weight basis and therefore appears to be a relevant vehicle for the delivery of LPS during meningitis.
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PMID:Haemophilus influenzae outer membrane vesicle-induced blood-brain barrier permeability during experimental meningitis. 278 92

The in vitro study of monocytes (Mo) poses several problems. Minor contamination with endotoxin (ET) of media and utensils as well as adherence to glass or plastic surfaces may activate the cells and cause pronounced production of monokines. Many commercially liquid culture media were found to contain ET in concentrations above 25 X 10(-12) g/ml. A simple system for the removal of ET from media and solutions was established by use of a commercially available Polymyxin B Sepharose gel. To measure the lipopolysaccharide (LPS) binding capacity of the gel, known concentrations of LPS were added to culture media, which were passed through a column consisting of the Polymyxin B Sepharose gel. The content of ET and added LPS in media was measured by the Limulus amoebocyte lysate (LAL) test before and after passage of the column. The LPS-binding capacity of the gel was approximately 2.4 X 10(-6) g/10 ml. The biological activity of contaminating ET and added LPS in media, before and after passage of the column, was also characterized by the capacity of the media to induce interleukin 1 (IL-1) secretion in human Mo cultures. The content of IL-1 in Mo culture supernatants was determined by the mouse thymocyte costimulatory (LAF) assay. By comparison of the activity of ET in these different biological systems, it was demonstrated that 15-20 X 10(-12) g/ml of ET stimulate human Mo cultures to IL-1 secretion.
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PMID:Removal of endotoxin from culture media by a polymyxin B sepharose column. The activity of contaminating endotoxin in culture media measured by the interleukin 1 inducing effect on human monocyte cultures and by the Limulus test. 282 97

To elucidate the function of the reticuloendothelial system of liver in hepatic injury, we investigated the effect of endotoxins on superoxide anion (O-2) generating capacity and lysosomal enzyme activities of Kupffer cells isolated from rats treated with galactosamine (Gal N), with Gal N supplemented with polymyxin B (Polymyxin B-Gal N), with lipopolysaccharide (LPS) and from control rats. After collagenase digestion of the liver and centrifugation over metrizamide gradient, Kupffer cells were prepared by the dish adherence procedure. O-2 production by the cells was examined as chemiluminescence during phagocytosis of latex particles and beta-glucuronidase activities were analyzed. High titers of endotoxemia were detected in LPS and Gal N rats by limulus test, while a low endotoxemia titer was found in Polymyxin B-Gal N rats. Hepatocyte damage was found in Gal N rats, but little was recognized in LPS and Polymyxin B-Gal N rats. In the latter groups, Kupffer cells, activated by endotoxins, showed the enhancement of chemiluminescence and a release of lysosomal enzyme. Though lysosomal enzyme was released from Kupffer cells in Gal N rats, chemiluminescence was slightly suppressed in spite of the high titer of endotoxemia. These results appear to be related to the consumption of O-2 during liver injury. The functional state of Kupffer cells was thus changed by the grade of endotoxemia and hepatic injury.
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PMID:Superoxide anion generating capacity and lysosomal enzyme activities of Kupffer cells in galactosamine induced hepatitis. 301 77

The effect of lipopolysaccharide (LPS) on the lymphokine (LK)-dependent activation of murine peritoneal macrophages for intracellular killing of Leishmania enriettii parasites was investigated. Exposure to LPS alone did not induce macrophages to kill the parasite. In the presence of LK or recombinant interferon-gamma, however, which by themselves rendered the macrophages only weakly cytotoxic, considerable stimulation of intracellular parasite killing was achieved already at a LPS concentration of 1 ng/ml. The response to LPS was of the same magnitude in macrophages tested for intracellular killing as in parallel assays of extracellular cytolysis of target cells. Acquisition of leishmanicidal activity by macrophages exposed to LK and LPS correlated with stimulation of the respiratory burst, as shown by increased hexose monophosphate shunt levels, and priming for elevated chemiluminescence and O2- and H2O2 production. Polymyxin B blocked both this LPS-dependent metabolic activity and intracellular parasite destruction. Intracellular killing was, however, not solely dependent on oxidative metabolism of macrophages since in the absence of LK, LPS stimulated respiratory burst activity, yet no intracellular killing was observed, and triggering of the respiratory burst by phorbol myristate acetate or zymosan did not affect intracellular parasite survival. These results suggest that, in this experimental model, efficient intracellular parasite killing depends both on increased production of oxygen metabolites and on the availability of so far unidentified factor(s), the synthesis of which requires exposure of macrophages to both LK and LPS.
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PMID:Effect of lipopolysaccharide on intracellular killing of Leishmania enriettii and correlation with macrophage oxidative metabolism. 303 Jul 68


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