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

We specifically investigated the significance of antibodies directed against pure preparations of lipopolysaccharide antigens and also against elastase of Pseudomonas aeruginosa. Antibodies were detected by an indirect enzyme-linked immunosorbent assay technique both in serum (IgG) and in sputum (sIgA). Patients with cystic fibrosis (CF) chronically infected with Ps. aeruginosa had significantly higher antibody titers both in serum and sputum than CF patients or non-CF persons not colonized with Ps. aeruginosa. There were differences in the antibody spectrum between the colonized CF group and the two non-colonized control group. The sensitivity was highest for homologous O-specific IgG in serum (91.9%), followed by homologous O-specific sIgA in sputum (79.4%) and sIgA anti-elastase in sputum (66.2%). O-specific IgG antibodies in serum indicate a previous contact with various O-antigens of Ps. aeruginosa rather than reflect the present condition of the patient. In the evaluation of the current status sIgA O-specific antibodies in sputum are an appropriate indicator, with titers increasing during acute exacerbations and decreasing to normal values subsequently.
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PMID:Significance of immunologic factors in cystic fibrosis. 245 29

The relationship among complement consumption, C3 deposition, and C3 fragmentation pattern was compared for serum-sensitive (Sers) and serum-resistant (Serr) strains of Pseudomonas aeruginosa. The Sers strains, which were mucoid strains derived from patients with cystic fibrosis, had lipopolysaccharide deficient in O-antigen side chains. These organisms generally activated much less complement per organism than their Serr counterparts, characterized by the presence of lipopolysaccharide with long lipopolysaccharide O side chains. Surprisingly, however, although the Serr strains consumed more total hemolytic complement, less C3 was deposited onto the surface of these strains than onto that of the Sers strains. Maximal C3 binding required the participation of both the classical and alternative complement pathways, although classical complement pathway involvement was more important for Serr strains. Finally, while more than half of the C3 deposited on most Sers strains was in the form of C3b, most of the C3 on the Serr strains was in the form of iC3b, indicating a more rapid and extensive conversion of C3b to iC3b on the surface of these strains. Limited complement activation by Sers mucoid strains of P. aeruginosa may confer a selective survival advantage to these organisms in colonizing the airways of patients with cystic fibrosis.
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PMID:Complement activation and C3 binding by serum-sensitive and serum-resistant strains of Pseudomonas aeruginosa. 249 5

Alginates from nine mucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis were purified by repeated ethanol precipitation, nuclease digestion, anion-exchange chromatography, dialysis, and lyophilization. Uronic acid constituted 72% of the dry weight when mannuronolactone was used as the internal standard in the carbazole-borate assay for uronic acids. The average degree of acetylation was 16%, and the ratio of mannuronic acid to gluluronic acid was 4.7. No homopolymeric blocks of guluronic acid were found when analyzed by nuclear magnetic resonance spectroscopy. Contaminating proteins were denatured by heating, and during purification the content of protein relative to alginate fell from 566 to 0.9%. The content of lipopolysaccharide was 0.012%. No immunological or biological activity was attributable to the protein or lipopolysaccharide content as estimated by immunoblotting, enzyme-linked immunosorbent assay (ELISA), and a neutrophil chemotaxis assay. Rabbits were hyperimmunized with P. aeruginosa alginates and alginate from the seaweed Laminaria hyperborea, and an ELISA that detected alginate-specific antibodies was developed. Antibodies to P. aeruginosa alginate were detected by ELISA in 1:4,000 dilutions of serum from patients with cystic fibrosis with chronic P. aeruginosa lung infection. The serological cross-reactions between serum from the nine patients with cystic fibrosis and the corresponding P. aeruginosa alginates were investigated and showed considerable heterogeneity. This finding indicates that P. aeruginosa alginate from more than one P. aeruginosa strain should be used in serological tests. There was no serological cross-reactivity between P. aeruginosa and Laminaria hyperborea alginate in either rabbits or patients with cystic fibrosis.
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PMID:Purification, characterization, and immunological cross-reactivity of alginates produced by mucoid Pseudomonas aeruginosa from patients with cystic fibrosis. 249 89

The lipopolysaccharide (LPS) of Pseudomonas aeruginosa PAO1 contains two species of O polysaccharide termed A and B bands. The high-molecular-weight B-band LPS determines the O specificity of the bacterium, while the antigenically distinct A-band LPS consists of only shorter-chain polysaccharides. Seven hybridomas secreting A-band-specific monoclonal antibodies were produced and used to study the LPS of standard and clinical strains. Although A-band antibodies did not agglutinate any of the serotype strains presently in the International Antigenic Typing Scheme, Western immunoblots revealed that 11 of the 17 serotype strains possessed A-band LPS. In a group of 250 clinical isolates from patients with cystic fibrosis, 170 (68%) had A-band LPS on the basis of agglutination tests, but in silver-stained gels all were shown to be deficient in O-antigen-containing B band. Investigation of serial isolates from a single patient revealed a pattern of antigenic variation. During the course of the infection, serotypeable isolates became nontypeable, and the O antigen was replaced with A band as the major LPS antigen. These results suggest that A-band LPS may be the major LPS antigen in nontypeable clinical isolates and a common antigen among other P. aeruginosa strains.
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PMID:Occurrence of a common lipopolysaccharide antigen in standard and clinical strains of Pseudomonas aeruginosa. 250 56

Chronic lung infection in cystic fibrosis is characteristically associated with polyagglutinable, serum-sensitive, mucoid strains of Pseudomonas aeruginosa. Enzyme-linked immunosorbent assay (ELISA) methods for standard-free quantitation of immunoglobulin G (IgG) and IgM antibodies to P. aeruginosa lipopolysaccharides (LPSs) have been developed. We now report the development of assays for quantitation of monomer and dimer total IgA and IgA anti-LPS antibodies. Use of these methods in diagnosis of early chronic P. aeruginosa lung infection was assessed. IgG and IgA anti-LPS levels increased significantly at the onset of chronic infection and continued to increase to very high levels in the later stages of infection. IgM anti-LPS levels also rose at the onset of chronic infection but did not increase further. The function of true- and false-positive rates was illustrated by using various concentrations of IgG, IgA, and IgM anti-LPS for discrimination of patients. Values that gave optimum separations were used for statistical evaluation of the diagnostic sensitivities and specificities of anti-LPS antibody concentrations. The results obtained in these assays were compared with a diagnosis, based on the number of precipitins in crossed immunoelectrophoresis, of serum samples from cystic fibrosis patients. In 64 paired serum samples taken before and immediately after the onset of chronic infection, as defined by crossed immunoelectrophoresis precipitins, the predictive values of a positive ELISA were 86% for IgG and 89% for IgA. The predictive values for a negative ELISA were 98% for IgG and 97% for IgA. Results of the IgM anti-LPS ELISA had a lower predictive value. Immunoblotting and absorption studies showed that IgG anti-LPS antibodies were directed specifically against LPS of P. aeuruginosa. ELISAs were developed to determine the specific IgG sublclasses involved. The increase in IgG anti-LPS involved all four subclasses. Highest anti-LPS titers were seen with IgG1 and IgG4, but the largest relative increases were seen with IgG2 and IgG3.
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PMID:Antilipopolysaccharide antibodies and differential diagnosis of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis. 250 58

The development of resistance to ciprofloxacin in nine clinical isolates of Pseudomonas aeruginosa was investigated. Isolates had increases in minimal inhibitory concentrations (MICs) from 0.25 to 16 micrograms/ml. The isolates also became resistant to ofloxacin and norfloxacin, but did not show increases in MICs to aminoglycosides, antipseudomonas penicillins, or cephalosporins. One isolate from a patient with endocarditis showed a reduction in a 43-kD outer membrane protein and simultaneous increase in the imipenem MIC. This isolate also showed impaired uptake of ciprofloxacin. Respiratory isolates from cystic fibrosis patients did not show loss of outer membrane protein. MICs were lowered by ethylene diaminetetra-acetic acid, suggesting changes in lipopolysaccharide. Resistant isolates were synergistically inhibited by combinations of ciprofloxacin plus tobramycin or ceftazidime, but MICs remained beyond the achievable serum level.
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PMID:Resistance to ciprofloxacin appearing during therapy. 251 60

An enzyme-linked immunosorbent assay specific for flagellum type (a or b) of Pseudomonas aeruginosa was used to detect serum immunoglobulin antibodies in 98 random outpatients and 14 colonized cystic fibrosis patients. Antibodies were detected to both types of flagella in addition to M-2 lipopolysaccharide. Titers to both flagellar antigens (FlAg) were 10 to 100 times higher in cystic fibrosis patients than in random outpatients of a comparable age group. Mean antibody titers against b-type FlAg were 454 for outpatients (ages newborn to 21 years), whereas the mean titer for cystic fibrosis patients (ages 6 to 21 years) was 51,520. Titers against a-type FlAg were generally lower, with mean outpatient titers of 68 and mean cystic fibrosis patient titers of 34,323. Differences were also seen in antibody titer against M-2 lipopolysaccharide, but these differences did not correspond to M-2 FlAg titers. In 98 random outpatients (ages newborn to 86 years), FlAg titers generally increased with age. To demonstrate further specificity of the enzyme-linked immunosorbent assay for flagellum antibody, Western blots were performed with selected high-titer cystic fibrosis patient sera. Sera that had a high titer (greater than 25,600) for b- or a-type FlAg showed a corresponding reactive band. These results demonstrate that flagellum antibodies are produced in humans in response to P. aeruginosa infection.
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PMID:Pseudomonas aeruginosa flagellar antibodies in patients with cystic fibrosis. 251 26

Antibody opsonins from cystic fibrosis (CF) patients were investigated using nonmucoid and mucoid lipopolysaccharide (LPS) immunotype 1 Pseudomonas aeruginosa as bacterial ligands and PMN phagocytes. CF sera were compared to normal sera, polyvalent PA LPS hyperimmune globulin, and isotype switch variant monoclonal antibodies (MAbs) specific for type 1 PA LPS. Sera from PA-infected CF patients (CF PA+) had elevated levels of PA LPS and alginate IgG antibodies and promoted significantly greater antibody-dependent PMN chemiluminescence responses than sera from uninfected CF patients (CF PA-) or normal human sera (NHS). After adjustment for autologous IgG PA LPS antibody content, however, CF PA+ sera had less antibody-dependent opsonic activity than sera from CF PA- patients (P less than 0.025) or NHS (P less than 0.0025), suggesting qualitative opsonic defects of IgG PA LPS antibodies in CF PA+ sera. Antigen-specific immunoprecipitation of PA LPS antibodies enhanced opsonization by 40% of CF PA+ sera while uniformly reducing that from CF PA- sera (P less than 0.01), indicating LPS-specific nonopsonic antibodies in some CF PA+ sera. Alginate antibodies were not critical opsonins in most uninfected CF patient sera. PA LPS IgG antibodies isolated by immunoaffinity chromatography from NHS, hyperimmune globulin, and CF PA- sources were opsonic and had greater activity at equal antigen-binding concentration than identical antibodies isolated from infected CF patients (P less than 0.01-0.05); the majority of isolates from CF PA+ sera did not promote PMN oxidative responses above nonopsonic baseline. A potential isotypic basis for these findings was supported by differences in PMN responses to PA opsonized with MAbs of identical specificity but differing isotypes. PA LPS-specific IgG antibodies inhibiting PMN oxidative responses in infected patient sera demonstrate antigen-specific immunomodulation of host responses by chronic bacterial parasitism in CF, which may play a role in the pathophysiology of lung disease.
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PMID:Nonopsonic antibodies in cystic fibrosis. Pseudomonas aeruginosa lipopolysaccharide-specific immunoglobulin G antibodies from infected patient sera inhibit neutrophil oxidative responses. 251 30

We examined the functional importance of immunoglobulin polypeptide fragments generated by Pseudomonas aeruginosa elastase (Pseudomonas elastase). The purpose of this study was to determine whether the elastase produced by Pseudomonas aeruginosa cleaves human IgG into immune fragments that functionally inhibit opsonophagocytosis. Our results confirm that IgG isolated from patients with cystic fibrosis (CF) incubated with purified pseudomonas elastase results in the generation of two major polypeptide fragments and that, furthermore, these fragments significantly inhibit bacterial uptake by human neutrophils. After 75 minutes bacterial uptake was six times greater when intact IgG was used as an opsonin (uptake 90.2% +/- 18.6% SEM) compared with a IgG was used as an opsonin (uptake 90.2% +/- 18.6% SEM) compared with a mixture of pseudomonas-lipopolysaccharide-reactive Fab and F(ab')2 fragments generated by pseudomonas elastase (uptake 15.4% +/- 0.8% SEM, p less than 0.001). Hydrolyzed CF IgG antibodies consistently resulted in a level of bacterial uptake less than that of normal saline negative controls (NS): (at 10 minutes, NS 26.6% vs CF 16.8%, p less than 0.05; at 75 minutes, NS 28.2% vs CF 15.4%, p less than 0.01. This suggests that the immune polypeptides are active inhibitors of the essential neutrophil phagocyte-bacterial cell interaction. Intact immune IgG reversed the defect in opsonophagocytosis. When intact IgG was mixed with IgG fragments the phagocytic rates increased directly with increasing amounts of intact IgG. We conclude that the elastase exoproduct secreted by Pseudomonas aeruginosa is capable of cleaving IgG into functionally important fragments that inhibit bacterial uptake. Furthermore, this inhibition can be overcome by increasing amounts of a commercially available preparation of intact immune IgG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional importance of cystic fibrosis immunoglobulin G fragments generated by Pseudomonas aeruginosa elastase. 251 65

A method for identification of the components of immune complexes would increase our understanding of the pathogenesis of chronic diseases such as Pseudomonas aeruginosa lung infection in cystic fibrosis. Capillary tube, gel diffusion and turbidimetric methods of determining immune complex formation were investigated with antigens from P. aeruginosa and the homologous rabbit antisera. Visible complexes were formed in the first two methods with flagella antigens. Purified lipopolysaccharide from P. aeruginosa would not form visible precipitates and a rapid and economical turbidimetric method was developed with 96-well microtiter plates. Larger quantities of immune complexes were formed in vitro with antigen/antibody ratios determined by the above methods. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting (Western blotting) were evaluated and found to be useful in determining the antigen and antibody components of these immune complexes.
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PMID:Determination of the components of immune complexes made in vitro with antigens derived from Pseudomonas aeruginosa. 256 92


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