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

Both monoclonal antibody (MAb) and polyclonal antibody (PAb) directed against the shared core/lipid A region of lipopolysaccharide (LPS) (endotoxin) provide protection during experimental gram-negative bacterial sepsis. Although these preparations have not been compared, clinical trials administering either preparation to septic patients have been instituted. The core/lipid A region of LPS represents an antigenic domain common to many, if not all, gram-negative microbes, and thus represents an ideal target site for antibody binding. We sought to determine (1) the protective capacity of similarly reactive IgG anti-core LPS/lipid A MAbs and PAbs, (2) whether the timing of administration was important, and (3) whether either would act additively with antimicrobial agents. Antibody was administered intravenously to outbred mice, and Escherichia coli 0111:B4 was then administered intravenously or intraperitoneally with hemoglobin. Monoclonal antibodies and PAbs were equally protective, and protection was maximized by pretreatment, although the effect extended to four hours after bacterial challenge. Both MAbs and PAbs acted in concert with gentamicin hydrochloride to further reduce lethality. We concluded that MAbs and PAbs were equally protective and that clinical utility may eventually be dictated by ease and cost of antibody production.
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PMID:Protective capacity of polyclonal and monoclonal antibodies directed against endotoxin during experimental sepsis. 317 88

From birth mice received diets containing copper at 0.5, 1, 2 or 6 mg/kg diet. At 8 wk of age they were killed and copper status and immune responsiveness were determined. Only the groups that received copper at 0.5 or 1 mg/kg showed signs of copper deficiency, such as reduced serum ceruloplasmin, hemoglobin, hematocrit and red blood cell counts and characteristic changes in organ pathology. Body and lymphoid organ weights were altered in the groups that received copper at 0.5 or 1 mg/kg. Males were more severely affected than females. A dose-related reduction in splenic T-cell subpopulations was noted in the 0.5 and 1 mg/kg groups. Responses to lipopolysaccharide challenge were reduced, and an increase in spontaneous cycling cells was noted in the groups receiving copper at 0.5 or 1 mg/kg. Only the group receiving copper at 0.5 mg/kg had increased stem cell activity; this increase was probably due to increased erythropoiesis to meet increased demands for red blood cells in this group. These data indicate that only groups receiving copper at 0.5 or 1 mg/kg in the diet were depleted and marginally depleted in copper, respectively, and that immune hyporesponsiveness differs between the depleted and marginally depleted groups.
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PMID:Severe or marginal copper deficiency results in a graded reduction in immune status in mice. 326 38

Leukopenic, immunosuppressed recipients of solid organ allografts are at high risk for gram-negative bacterial sepsis, and mortality remains unacceptably high (greater than 30%). The purpose of this study was to determine whether murine monoclonal antibody (MAb) directed against lipopolysaccharide (LPS, endotoxin) would reduce lethality caused by a septic insult in immunosuppressed mice, and to determine if a specific antibody class would prove more efficacious in this setting. Two MAbs (3-H9, IgG3; 7-B5, IgM) were selected that reacted by ELISA, immunodot blot, and Western blot analysis against the O antigen polysaccharide portion of Escherichia coli 0111:B4 LPS. The 3-H9 MAb, 7B-5 MAb, or sterile saline was administered i.v. to normal or neutropenic Swiss-Webster mice immediately prior to an E coli 0111:B4 bacterial (i.v. or i.p. plus hemoglobin) or LPS (i.v.) challenge. In normal mice, administration of 3-H9 MAb or 7-B5 MAb i.v. immediately prior to a bacterial or endotoxin challenge resulted in a significant increase in the LD50. Neutropenia lowered the LD50 by nearly one log10 in both the bacteremia and peritonitis models. Both MAbs provided similar protection, raising the LD50 one log10 in neutropenic mice. Thus neutropenic animals receiving either MAb had a mortality nearly identical to that of normal animals receiving saline. No significant difference between the protective capacity of these MAbs was noted in any of the three models. These studies demonstrate that MAbs directed against LPS exert protection during gram-negative bacterial sepsis in either normal or neutropenic animals. In addition, the particular IgG and IgM MAbs examined provided similar protective capacity. Antibody directed against LPS may provide an additive form of therapy that may serve to decrease lethality during clinical gram-negative sepsis in immunosuppressed patients.
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PMID:Antibody immunotherapy of gram-negative bacterial sepsis in an immunosuppressed animal model. 327 38

An antiserum with a high content of antibodies, binding to the Gram-negative lipopolysaccharide core region, was prepared by immunizing rabbits with the rough Escherichia coli mutant J5. This antiserum was capable of protecting mice against lethal challenge doses of E. coli 0 111:B4 in a mouse model where the animals were compromised by means of mucin plus hemoglobin (LD 50 = 10(3) bacteria). However, no protection was observed in a non-compromised mouse model (LD 50 = 10(7) bacteria). This observation might explain why in the past so many discrepant results have been obtained in mouse protection studies with cross-reactive antisera.
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PMID:Use of mucin and hemoglobin in experimental murine gram-negative bacteremia enhances the immunoprotective action of antibodies reactive with the lipopolysaccharide core region. 354 72

A lupus-like disease characterized by a severe immune complex glomerulonephritis and IgG autoantibody production was induced in (C57BL/6 X DBA/2)F1 mice by injection of parental DBA/2 lymphoid cells. The ensuing graft-vs-host (GVH) reaction resulted in a 10- and a 100-fold increase in serum IgG antibody levels to denatured DNA and total histones, respectively, compared with that in F1----F1 control mice. The level of anti-DNA antibodies peaked 2 wk after injection of DBA/2 cells and preceded peak anti-histone levels by approximately 2 wk. Anti-histone antibodies were generated predominantly to histones H1, H2A, and H2B, a profile different from that observed in NZB/NZW and MRL-lpr/lpr mice. The marked increase in IgG antinuclear antibodies did not correlate with increases in total IgG serum levels and was not associated with comparable increases in antibodies to transferrin, hemoglobin, fibrinogen, or thyroglobulin. Selective autoantibody production was also observed in vitro, wherein GVH spleen cells produced high levels of IgG antibodies to total histones and denatured DNA but not to these non-nuclear protein antigens. In contrast, spleen cells stimulated in vitro with lipopolysaccharide produced equivalent amounts of antibodies to all antigens tested. Our results are in agreement with those of other investigators and collectively suggest that IgG autoantibodies in GVH disease, and possibly in spontaneous lupus-like disease, are not secondary to a generalized B cell activation, but may be selectively generated in response to self antigens with unique configurational properties.
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PMID:Autoimmunization in murine graft-vs-host disease. I. Selective production of antibodies to histones and DNA. 387 58

The potential immunoprotective role of antiserum to an Escherichia coli J5 mutant derived from E. coli O111:B4 was demonstrated in an experimental mouse model. Overwhelming bacterial inocula masked the effects of cross-reactive immunoprotection due to antiserum to strain J5. Enhanced bacterial clearance was observed in mice receiving antiserum to strain J5 in sublethal infections but not from lethal doses. Incorporation of hemoglobin with the bacterial inocula decreased the 50% lethal dose of challenge organisms, allowing the demonstration of protective activity of antiserum to strain J5 in lethal infection. Pretreatment of mice with antiserum to strain J5 did not protect against lethal doses of endotoxin. The protective factor was demonstrated by exhaustive adsorption experiments to be an antibody specific for strain J5 lipopolysaccharide. The protective activity of antiserum to strain J5 was abolished only after adsorption with strain J5 lipopolysaccharide but not with Salmonella typhimurium mutants with or without enterobacterial common antigen.
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PMID:Cross-reactive immunoprotective antibodies to Escherichia coli O111 rough mutant J5. 388 75

To study the role of antibodies in promoting survival during gram-negative bacterial sepsis, we have developed several murine monoclonal antibodies (MAbs). One MAb (5B10) reacted in an enzyme-linked immunosorbent assay with only a single organism (Escherichia coli 0111:B4), while the other (8A1) reacted to all gram-negative whole-cell and lipopolysaccharide (LPS) antigens examined. Either 5B10 MAb, 8A1 MAb, or sterile saline solution was administered intravenously to outbred male Swiss-Webster mice immediately before one of three challenges: (1) viable bacteria intravenously, (2) viable bacteria with hemoglobin intraperitoneally, or (3) intravenous actinomycin D plus LPS. 5B10 MAb provided significant protection against either an E. coli 0111:B4 bacterial or LPS challenge but not against any other organism or type of LPS. 8A1 MAb provided protection against several challenge bacteria (intravenously or intraperitoneally) and against all types of LPS studied except Pseudomonas aeruginosa LPS. A higher dose (2 mg) of cross-reactive antibody (8A1 MAb) was required to produce protection when compared with the type-specific protection produced with 5B10 MAb (0.1 mg). Although ideal antibody therapy would consist of directing a specific MAb against a single microorganism, the acute nature of the disease process and time required to prepare reagents may preclude the use of type-specific MAbs. We believe that the cross-reactive and cross-protective capacity of 8A1 MAb or a similar MAb may be useful in averting the lethal effects of clinical gram-negative bacterial sepsis and warrants testing in the clinical setting.
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PMID:Efficacy of type-specific and cross-reactive murine monoclonal antibodies directed against endotoxin during experimental sepsis. 389 40

The activity of 38 calves aged 15-30 days of the Simenthal breed and of crosses with Ireshire was studied before and after transportaton at a distance of 38-100 km. It was established that transportation causes fatigue, thirst and a weight reduction of 4.3 kg, due to loss of liquid in the calf's organism. Caughing, soft faeces, even diarrhea, 1.5 degrees C higher rectal temperature, and 3.0 degrees C lower skin temperature, were recorded. the MacClure--Oldridge test proved twice as fast. As a result of hemoconcentration hemoglobin and hematocrite were higher. Eosinopaenia and neutrophylia with a nuclear deviation to the left similar to the reaction of experimentally induced lipopolysaccharide fever were established. On the 72d hour lymphocytosis and an enhanced lymhocytal index were observed. Transportation led to 15-18% higher number of phagocyted neutrophyls, 30-35% higher Wright number and nearly two times higher total blood phagocytal ability. Seventy two hours after two times higher total blood phagocytal ability. Seventy two hours after transportation the total blood phagocytal ability was reduced 15%. Another effect of calf transportation was the reduced total immunological reactivity, scored by the skin test of Yoffe.
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PMID:[Reactivity changes in calves during transportation]. 741 35

Recent demonstration of cytokine-inducible production of nitric oxide (NO) in vascular smooth muscle cells (VSMC) from rat aorta has implicated VSMC-derived NO as a key mediator of hypotension in septic shock. Our studies to determine whether an inducible NO pathway exists in human VSMC have revealed a novel cytokine-inducible, NO-independent pathway of guanylate cyclase activation in VSMC from human saphenous vein (HSVSMC). Interleukin 1 (IL-1), tumor necrosis factor (TNF), interferon gamma (IFN-gamma) and Escherichia coli lipopolysaccharide (LPS) increased cGMP at 24 h, whereas IL-2 and IL-6 were ineffective. The effect of IL-1 on cyclic guanosine 3',5'-monophosphate (cGMP) was delayed, occurring after 6 h of exposure, and was maximal after 10 h. Methylene blue and LY83583 reversed the IL-1-induced increase in cGMP, suggesting that it was mediated by activation of soluble guanylate cyclase. However, IL-1-induced cGMP in HSVSMC was not inhibited by extracellular hemoglobin. Also, the effect of IL-1 on cGMP was not reversed by nitro- or methyl-substituted L-arginine analogs, aminoguanidine, or diphenyleneiodonium, all of which inhibit IL-1-induced NO synthase in rat aortic VSMC (RAVSMC). IL-1-induced cGMP in HSVSMC was also independent of tetrahydrobiopterin and extracellular L-arginine, as it was not affected by 2,4-diamino-6-hydroxyprytimidine, an inhibitor of tetrahydrobiopterin biosynthesis, and was similar in L-arginine-free and L-arginine-containing media. Analysis of NO synthase mRNA with the use of polymerase chain reaction indicates that levels of mRNA for inducible NO synthase are several orders of magnitude lower in IL-1-treated human HSVSMC than in IL-1-treated RAVSMC. IL-1-induced cGMP was also NO independent in human umbilical artery VSMC, and NO dependent in rat vena cava VSMC. Together these results indicate that IL-1 activates a novel NO-independent pathway of soluble guanylate cyclase activation in human VSMC.
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PMID:Interleukin 1 activates soluble guanylate cyclase in human vascular smooth muscle cells through a novel nitric oxide-independent pathway. 750 3

The effects of L-arginine on the adrenergic responses to either electrical transmural stimulation or phenylephrine were studied in isolated endothelium-denuded strips of rat tail arteries treated with lipopolysaccharide for 6 h in vitro. L-arginine did not relax the strips precontracted by phenylephrine. However, the adrenergic contractions induced by electrical transmural stimulation were significantly inhibited by the addition of L-arginine. This inhibitory effect was reversed by NG-nitro-L-arginine (a nitric oxide synthase inhibitor) or methylene blue (a soluble guanylate cyclase inhibitor) but was not affected by hemoglobin (a scavenger of nitric oxide). These results indicate that the adrenergic neurogenic contractions may be directly modulated by nitric oxide derived from the sympathetic nerves and/or neighboring cells in the lipopolysaccharide-treated rat tail arteries, and the nitric oxide production may be associated with the reduction of sympathetic tone in sepsis.
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PMID:Selective inhibition of sympathetic nerve-mediated contraction by L-arginine in lipopolysaccharide-treated tail artery of rats. 753 6


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