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)

Lymphocytes from healthy volunteers and from cystic fibrosis patients were transformed with Epstein-Barr virus and cultured at a limiting dilution to generate lymphoblastoid cell lines that secreted human monoclonal antibodies specific for lipopolysaccharide (LPS) from Pseudomonas aeruginosa. Three cell lines (RM5, FDD7, and 11F9) produced immunoglobulin M (IgM) antibody species that reacted specifically with P. aeruginosa Fisher immunotypes 2, 4, and 5, respectively, and with LPS extracted from these immunotypes. A fourth cell line (9H10) produced a single IgM antibody species that recognized P. aeruginosa immunotypes 3, 6, and 7 and LPS extracted from them. Monoclonal antibodies secreted by cell lines RM5, FDD7, and 11F9 protected neutropenic mice prophylactically against challenge with P. aeruginosa immunotypes 2, 4, and 5, and those secreted by 9H10 protected against P. aeruginosa immunotypes 3 and 6 but did not protect against immunotype 7. In vivo experiments indicated that antibodies protected mice against infection by increasing the rate of bacterial clearance.
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PMID:Human monoclonal antibodies that protect mice against challenge with Pseudomonas aeruginosa. 313 64

A clinical isolate of Pseudomonas cepacia from a cystic fibrosis patient was examined for its ability to produce extracellular toxic material. The organism was grown to stationary phase in a defined medium and toxic material was isolated by ultrafiltration, ion-exchange chromatography on DEAE-Sephacel and gel-filtration chromatography on Sepharose 4B. It consisted of a surface carbohydrate antigen, lipopolysaccharide and protein, and had an LD50 (when injected intraperitoneally into mice) of 395 +/- 20 micrograms. The toxicity appeared to be associated with the lipopolysaccharide portion of the complex, because boiling for 15 min and exposure to proteolytic enzymes had no effect on toxicity. However, saponification destroyed the toxicity of the compound. Studies employing radial immunodiffusion with the sera of mice infected with this organism demonstrated production of the complex in vivo at levels approaching those sufficient to produce death. When sublethal amounts of this complex were placed in the lungs of specific-pathogen-free rats, the lung pathology observed after 12, 24, 36 and 48 h was extensive. However, antibody generated in rabbits against this material could protect mice against the complex, as well as against challenge by the homologous organism. These data indicate that extracellular toxic material produced by P. cepacia may be responsible for the lethality and lung tissue destruction normally associated with an active pneumonia caused by this organism.
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PMID:The importance of extracellular antigens in Pseudomonas cepacia infections. 313 8

Cell-surface polysaccharide antigens of Pseudomonas aeruginosa are important determinants of pathogenicity and represent target antigens for the development of vaccines. Two major and distinct cell-surface polysaccharides are expressed by different strains of P. aeruginosa: the serotype determinant located on the O polysaccharide side chain of the lipopolysaccharide and mucoid exopolysaccharide (MEP), an antigen usually made by isolates of P. aeruginosa from patients with cystic fibrosis. The serotype determinant has been isolated in a high-molecular-weight, non-toxic, immunogenic form known as high-molecular-weight polysaccharide. High-molecular-weight polysaccharide is safe and immunogenic in humans and elicits T cell immunity to P. aeruginosa infection in animals. Purified MEP antigen has been shown to be immunogenic in animals, and patients with cystic fibrosis colonized with mucoid P. aeruginosa respond to MEP with the production of high-titered serum antibody. In spite of brisk immune responses of patients with cystic fibrosis to MEP, they are unable to deal with the chronic respiratory colonization by mucoid P. aeruginosa. An association has been established between the presence of opsonic-killing antibody to MEP and the lack of colonization of older patients with cystic fibrosis with P. aeruginosa.
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PMID:Polysaccharide antigens of Pseudomonas aeruginosa. 314 17

The systemic humoral immune response in cystic fibrosis (CF) to outer membrane (OM) proteins of Pseudomonas aeruginosa was investigated as a function of the time of colonization by immunoblotting. OM proteins were prepared from bacteria grown in ion-sufficient, magnesium-depleted, and iron-deficient media. The location of proteins F, H, and I on the blots was verified by monoclonal antibodies. Proteins H2 and H1 were differentiated by the overexpression of H1 under magnesium depletion. Iron-regulated membrane proteins (IRMPs) were recognized by their overproduction under iron limitation. Plasma samples from 43 CF patients and ten healthy adults were analyzed after preadsorption with lipopolysaccharide (LPS). Within the first year of colonization, only two to six specific plasma antibodies to OM proteins were produced. After a strong increase during the second year, long-lasting levels were seen in the majority of patients. Large variations of the immune response were noted among the patients. The number of specific antibodies to different OM proteins correlated with the severity of the course of lung disease. At maximum 38 immunostained bands were observed. Proteins H and I were the earliest antigens amongst the major OM proteins. During the second year, antibodies directed to protein F became detectable. IRMPs which indicate the growth of P. aeruginosa under iron deprivation were only recognized by plasma samples from chronically colonized CF patients with advanced lung disease.
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PMID:Immune response in cystic fibrosis to outer membrane proteins of Pseudomonas aeruginosa. 314 71

It has been observed that each strain of the Pseudomonas aeruginosa species harbours the so-called polyagglutinable antigen (PA). Some strains may produce it in a form which is linked to the core moiety of lipopolysaccharide (LPS) and this type of PA can thus be detected by passive haemagglutination using the isolated LPS as coating antigen. Other strains synthesize PA exclusively in a free form, which is also coextractable with LPS, its presence can, however, be demonstrated by the haemagglutination inhibition test. From a polyagglutinable strain of P. aeruginosa an R-type LPS was isolated having the core-linked PA. This LPS preparation was highly immunogenic with regard to its PA moiety. The core-bound PA seems to exert an immunosuppression on the core region, hence, the polyagglutinable strains isolated from cystic fibrosis patients only engender anti-PA antibodies, whereas antibodies against both, side chain and core region of LPS, are not engendered. The mucoid exopolysaccharide also contains the PA which could possibly play an important role in the patient by protecting P. aeruginosa cells against anti-PA antibodies.
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PMID:Structural relationship between the polyagglutinable antigen and the core polysaccharide of Pseudomonas aeruginosa. 315 44

Patients with cystic fibrosis (CF) have impaired natural (preinfection) IgG2 antibody responses to Pseudomonas aeruginosa lipopolysaccharide. To investigate the basis for this defect, we measured natural IgG and IgG1-4 antibody levels to Haemophilus influenzae type b polyribophosphate (PRP) and tetanus toxoid by enzyme-linked immunosorbent assay in 24 adult CF patients and 20 normal controls. Immunoglobulin heavy- and light-chain allotypes were determined on 146 Caucasian CF patients and 96 controls. The tetanus toxoid-specific IgG response was predominantly IgG1. CF and control subjects had similar IgG and IgG1 antibody levels. The PRP-specific IgG response was predominantly IgG2. In contrast to tetanus toxoid results, CF patients had lower geometric mean level of PRP-specific IgG compared to normal controls (p = 0.0036). ELISA results were confirmed by liquid-phase 3H-PRP-binding assay: CF patients had a geometric mean serum antibody level of 395 versus 922 ng/ml in controls (p = 0.0044). PRP-specific IgG2 levels were also depressed in CF patients (p = 0.03). CF patients had a lower prevalence of the A2m(2) allotype than the local racially matched control sample (p less than 0.025). Other allotype prevalences including G2m(n) and Km(1) were similar. Impaired IgG2 antibody responses to microbial polysaccharide surface antigens in CF patients might predispose them to persistent endobronchial infection and lead to production of nonopsonizing isotype responses. The potential role of A2m(2), coded for in the H chain locus on chromosome 14, is unknown, but could be related to mucosal IgA2 antibody responses.
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PMID:Altered antibody isotype in cystic fibrosis: impaired natural antibody response to polysaccharide antigens. 350 65

Patients with cystic fibrosis (CF) whose respiratory tracts are colonized with Pseudomonas aeruginosa (PA) may develop a specific opsonic deficiency for alveolar macrophage phagocytosis of PA. We examined the possible role of altered antibody (Ab) isotype in this phenomenon by measuring serum levels and distribution of IgG and IgG subclass Ab (IgG1, IgG2, IgG3, and IgG4) to the major opsonic immunodeterminant, serotype-specific lipopolysaccharide (LPS), by means of enzyme-linked immunosorbent assays employing monoclonal secondary antibodies, and comparing these results to the serum opsonic capacity in an in vitro murine alveolar macrophage phagocytic assay. Twenty-one patients with CF who were colonized with PA had approximately a 30-fold elevation of PA LPS IgG Ab levels and higher IgG subclass 1-4 Ab compared to 10 uncolonized patients with CF and 11 healthy controls (p less than 0.05-0.0005 depending on the isotype). Colonized patients with CF had a shift in PA LPS Ab distribution toward IgG3 compared to uncolonized patients with CF (p less than 0.02). A surprising finding was that uncolonized patients with CF had lower levels (p less than 0.05) and proportion (p less than 0.002) of PA LPS IgG2 Ab than controls, with an apparent shift to higher levels and proportion of PA LPS IgG4 (p less than 0.01). Serum from colonized patients with CF showed diminished opsonic capacity for phagocytosis of PA compared to uncolonized patients and controls (p less than 0.005), with 42% showing inhibitory activity. Functional Ab was also found to be inhibitory at high (greater than 500 ng/ml) concentrations. Serum opsonic capacity appeared to include a noncomplement cofactor for optimal activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered antibody isotype in cystic fibrosis: possible role in opsonic deficiency. 371 55

Hypergammaglobulinemia, chronic endobronchial infection with Pseudomonas aeruginosa (PA), and the resulting systemic humoral immune response to PA are each associated with worsened clinical status and prognosis in patients with cystic fibrosis (CF). Major serum immunoglobulin isotype levels (IgG, IgA, IgM, and IgG1-4 subclasses) were measured in 31 CF patients and ten control subjects. Immunoglobulin levels were related to airway infection with PA and the resulting IgG antibody response against PA lipopolysaccharide (LPS). Hyperimmunoglobulinemia G was present with elevated IgG1 and IgG2 in 48 percent, IgG3 in 52 percent, and IgG4 in 42 percent of CF patients. The PA infection was associated with striking increases in IgG2. IgG2 levels correlated well with IgG2 antibodies to PA LPS (r = +0.70, p less than 0.001). However, even CF patients who were not infected with PA had an increased prevalence of high IgG3 (p less than 0.05) and IgG4 (p less than 0.01). The PA infection thus appears to be a major, but not the only factor causing hypergammaglobulinemia in CF.
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PMID:Hypergammaglobulinemia in cystic fibrosis. Role of Pseudomonas endobronchial infection. 382 44

Mucoid exopolysaccharide isolated from Pseudomonas aeruginosa obtained from colonized cystic fibrosis patients was found to be a potent mitogen for mouse lymphocytes. The responding lymphocyte was a B cell, and we found no evidence that T cell could proliferate or synergize with B cells in response to the mucoid exopolysaccharide. Proliferation was not inhibitable by polymyxin B, which blocks lipopolysaccharide (LPS)-induced proliferation, indicating that a minor LPS contaminant in the purified exopolysaccharide was not the mitogenic component. Mucoid exopolysaccharide induced secretion of IgG, suggesting that it is polyclonal mitogen. It also induced splenic adherent cells (macrophages) to produce interleukin 1. We propose that mucoid exopolysaccharide produced by P. aeruginosa present in the lungs of cystic fibrosis patients may have potent in vivo consequences resulting in aberrant immunoregulation and inhibition of effective immune elimination of P. aeruginosa.
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PMID:Polyclonal B cell stimulation and interleukin 1 induction by the mucoid exopolysaccharide of Pseudomonas aeruginosa associated with cystic fibrosis. 392 Mar 10

Twenty Pseudomonas aeruginosa strains isolated from patients with cystic fibrosis in good and poor clinical condition were typed by the American Scientific (Difco Laboratories, Detroit, Mich.) Typing Scheme. Only five strains were agglutinated with a single typing serum. Ten strains were agglutinated with more than one serum, and five were not agglutinated with any serum, suggesting some type of lipopolysaccharide alteration in the majority of these strains. Of the strains from patients in good clinical condition, 72% demonstrated proteolytic activity, while 60% of the strains from patients in poor clinical condition demonstrated no proteolytic activity. Twenty-three cystic fibrosis strains of P. aeruginosa examined demonstrated reduced bacteremic virulence when compared with a virulent burn strain with a 50% lethal dose (LD50) of 1.5 X 10(1) CFU in an invasive burned mouse model. Ninety-two percent of the strains tested were avirulent at doses of 10(3) to 10(5) CFU. The LD50s were determined for 10 selected strains which exhibited specific important morphological and physiological deficiencies. Five of the strains tested gave LD50s greater than 10(6) CFU. Reduced virulence of these strains was associated with loss of two or more physiological characteristics associated with virulence. The cystic fibrosis strains of P. aeruginosa which morphologically and physiologically resembled the virulent burn strain were the most virulent (LD50s of 10(2) to 10(4). Results suggest that some degree of virulence is associated only with classic strains prevalent in early infections. The data suggest that a selection transition occurs in the lungs of patients with cystic fibrosis that favors P. aeruginosa avirulence. The avirulent state may be caused by alterations in the cell envelope, including associated factors such as motility and chemotaxis and protease production.
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PMID:Avirulence and altered physiological properties of cystic fibrosis strains of Pseudomonas aeruginosa. 393 13


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