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

Cirrhotic rats have decreased pulmonary bactericidal activity and increased bacteremia after experimental pneumococcal pneumonia. To determine if this finding is due to impaired pulmonary recruitment of polymorphonuclear leukocytes (PMNL), bronchoalveolar lavage (BAL) was done on cirrhotic and normal rats after transtracheal challenge with pneumococcal types 3 and 1. Mean absolute numbers of recruited PMNL in BAL fluid (BALF) at 2, 4, 6, 8, and 24 h after 10(7) cfu of type 3 challenge were similar in cirrhotic and normal rats. In both groups, lower numbers of PMNL were recruited after challenge with 10(5) cfu of type 3. Type 1 pneumococci stimulated recruitment of similar mean absolute numbers of PMNL (x10(7] in BALF (cirrhotics vs. normals) at 24 h after challenges with 10(5) cfu (0.3 +/- 0.1 vs. 0.3 +/- 0.1) and 10(7) cfu (2.9 +/- 1.3 vs. 2.8 +/- 0.7). Peripheral blood PMNL from cirrhotic and normal rats did not differ in adherence to nylon wool columns or in chemotaxis toward lipopolysaccharide-activated normal rat serum. Thus the impaired pulmonary defense against pneumococcal pneumonia in cirrhosis is not due to deficient pulmonary PMNL recruitment.
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PMID:Pulmonary recruitment, adherence, and chemotaxis of neutrophils in a rat model of cirrhosis and pneumococcal pneumonia. 195 20

The phagocytosis of Haemophilus influenzae type b (Hib) by rat macrophages and the intracellular fate of ingested organisms was investigated using an acridine orange-crystal violet assay. There was a correlation between the ability of organisms to survive in macrophages in vitro and their ability to cause invasive disease. Encapsulated Hib survived and replicated within macrophages, whereas capsule-deficient mutants, although more susceptible to phagocytosis, were killed after ingestion. Differences in lipopolysaccharide also affected the ability of encapsulated Hib to survive in macrophages. The presence of viable intracellular organisms in macrophages in vivo may enhance the persistence of bacteremia and may also be important in mediating the entry of Hib into the central nervous system.
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PMID:Relationship between intracellular survival in macrophages and virulence of Haemophilus influenzae type b. 203 2

An overview of gram-negative sepsis is presented, and the need for improved treatment for this condition is emphasized. The availability of new and more potent antimicrobial agents has not substantially altered the mortality from sepsis and septic shock. Gram-negative infection, bacteremia, sepsis, and septic shock remain major clinical problems, particularly among hospitalized patients. The estimated incidence of gram-negative sepsis in the United States alone is 200,000 cases annually. The predominant pathogens are Escherichia coli, Klebsiella, and Pseudomonas aeruginosa. Mortality is strongly influenced by the host's clinical status and age and the development of shock; it may reach 90% in patients with rapidly fatal disease. Analysis of risk factors and use of criteria for categorizing severity of disease can be helpful in designing new treatments, identifying potential recipients of such agents, and evaluating outcome of therapy. Because bacterial endotoxin plays a pivotal role in triggering the biological cascade of mediators in the septic process, a new therapy has been developed, immunotherapy with monoclonal antibodies that neutralize lipopolysaccharide by binding to lipid A. Successful treatment of gram-negative sepsis requires appropriate patient identification and timely intervention. While antimicrobial agents remain important, monoclonal antibodies hold promise as a new therapeutic intervention.
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PMID:Overview of gram-negative sepsis. 227 77

Genes necessary for the expression and phase variation of lipopolysaccharide epitopes of a virulent Haemophilus influenzae type b isolate (RM.7004) are contained within two chromosomal loci designated lic-1 and lic-2. Mutations were introduced into both lic-1 and lic-2, and the virulence of the double mutant was compared with that of the wild type in infant rats. These mutations in RM.7004 resulted in a significantly reduced incidence of bacteremia following intranasal inoculation, although nasopharyngeal colonization was similar for the mutant and wild-type strains. In contrast, no differences in bacteremia were observed when the mutant and wild-type strains were inoculated intraperitoneally.
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PMID:Phase-variable lipopolysaccharide structures enhance the invasive capacity of Haemophilus influenzae. 240 71

Monoclonal IgM specific for the O18 antigen conferred passive protection to 1-week-old rats against bacteremia and killing after oral challenge with O18:K1 Escherichia coli. Specific protection of the pups was also achieved by immunizing the pregnant rats with purified O18 lipopolysaccharide. We suppose that most human newborns that are colonized by potentially invasive K1 E. coli are protected by the transplacental transfer of anti-lipopolysaccharide immunoglobulin G, and we suggest that treatment with such antibodies might in the future be considered a therapeutic option. Rat serum from 1-week-old animals had only about one-third of the complement hemolytic activity of adult rat serum. This low level of hemolytic activity correlated with a relatively poor bactericidal activity in antibody-dependent and antibody-independent bactericidal in vitro assays. Monoclonal anti-O18 immunoglobulin M, although protective in vivo and bactericidal when added to adult rat serum, only poorly inhibited the multiplication of O18:K1 cells in serum from 1-week-old rats. This suggests that other elements of host defense besides complement participate in antibody-mediated in vivo protection.
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PMID:Antibodies to O-antigen of lipopolysaccharide are protective against neonatal infection with Escherichia coli K1. 241 Mar 65

We studied a previously healthy 20-year-old woman who presented with gonococcal meningitis. The gonococcal isolate, HT-1, was prototrophic by auxotyping, was protein I serovar IB-1, and agglutinated with wheat germ lectin. This isolate differed from the proline-requiring, serovar IA-1 and IB-4, wheat germ-agglutination-negative gonococcal isolates recovered from three patients during a recent outbreak of gonococcal meningitis in Philadelphia. HT-1 was killed by normal pooled human sera (greater than or equal to 98% at 30 min) but not effectively killed by the convalescent-phase sera of the patient (greater than 30% survival at 30 min). Similar results were obtained when mucosal and cerebrospinal fluid isolates from a Philadelphia patient were exposed to these sera, but mucosal and blood isolates from another Philadelphia case showed increased resistance to killing by normal pooled human sera. Further characterization revealed multiple differences in outer membrane and cellular proteins and lipopolysaccharide between case isolates. Absence of the L8 lipopolysaccharide epitope was noted for all isolates. Sera of our patient were found to have low total hemolytic complement (CH100 = 21 U/ml; normal = 55 to 100 U/ml) due to deficiency of C8 (C8 less than 1,000 CH50 U/ml; normal = greater than or equal to 16,000 CH50 U/ml). This is the first reported case of gonococcal meningitis occurring in a patient with a terminal-complement deficiency. Gonococcal meningitis is a rare complication of gonococcal bacteremia. Both defects in host defenses (e.g., terminal-complement deficiency) and organisms with unusual virulence appear to contribute to the pathogenesis of this complication of gonococcal bacteremia.
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PMID:Comparison of isolates of Neisseria gonorrhoeae causing meningitis and report of gonococcal meningitis in a patient with C8 deficiency. 247 91

Serotype b strains of Haemophilus influenzae are strikingly more highly associated with episodes of invasive, life-threatening infection in young children than are strains of other serotypes, but the role that the capsule itself plays in determining this virulence has not been dissected away from that of possibly linked virulence determinants such as lipopolysaccharide (LPS). Using DNA from clinical isolates of all six serotypes (a-f) and a genetically-defined capsule-deficient recipient strain Rb-: 02, we constructed a series of capsular transformants otherwise identical with respect to outer-membrane protein and LPS subtype, biotype, and electrotype. Cloned DNA was also used to create type a and b transformants isogenic outside the capsulation locus to provide the most rigorous test to determine whether capsule alone modulates pathogenicity. Capsular transformants showed the same spectrum of virulence in an infant rat bacteremia/meningitis assay as wild-type strains, thus implicating the capsule polysaccharide as an independent determinant of virulence. Experiments in intact and splenectomised rats identified a critical role for type b capsule in enabling organisms to evade splenic clearance.
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PMID:The molecular basis of pathogenicity in Haemophilus influenzae: comparative virulence of genetically-related capsular transformants and correlation with changes at the capsulation locus cap. 261 36

Cytokines secreted in response to invading micro-organisms are important mediators of detrimental hemodynamic and metabolic changes in the host. To test whether cachectin/TNF plays a role in triggering release of other cytokines in the setting of infection, anesthetized baboons were passively immunized against systemic cachectin/TNF before infusion of a LD100 dose of live Escherichia coli. Bacteremia led to significant increases in circulating levels of cachectin/TNF, IL-1 beta, and IL-6. Although bacterial endotoxin/lipopolysaccharide is a potent stimulus for the synthesis and release of IL-1 and IL-6 in vitro, specific neutralization of cachectin/TNF in vivo with mAb pretreatment significantly attenuated both the IL-1 beta and the IL-6 responses despite fulminant overwhelming bacteremia. These data suggest that cachectin/TNF is essential for the initiation or amplification of IL-1 and IL-6 release during lethal gram-negative septic shock syndrome.
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PMID:Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia. 280 10

This study was undertaken in order to evaluate whether patients with bacteremia respond with antibodies directed towards two outer membrane components of Gram-negative bacteria. The antibody responses to the core of the lipopolysaccharide molecule (LPS) of the rough E. coli J5 mutant and to a purified outer membrane protein (porin) from Salmonella were studied in bacteremic patients. Two or three serum samples were consecutively collected from 77 patients having 82 episodes of bacteremia altogether, of these 50 were caused by bacteria of the genus Enterobacteriaceae. As controls, sera from 82 age and sex matched patients and 100 healthy blood donors were analysed. The antibody titers were assessed by enzyme-linked immunosorbent assays (ELISA). None of the patients with bacteremia responded with an increase in antibody level to the E. coli J5 rough LPS. This finding indicates that the core portion of the E. coli J5 LPS contains no antigenic epitopes immunologically cross-reactive with Gram-negative bacteria causing bacteremia. By contrast, 13 patients showed significant titer increases to the porin preparation derived from Salmonella. Twelve of these patients had bacteremia caused by Gram-negative organisms belonging to Enterobacteriaceae. One patient had bacteremia with Bacteroides fragilis but also suffered from a severe peritonitis with growth of both E. coli and Klebsiella. It is suggested that the measurement of antibody response to porin may be of value for differential serological diagnosis in patients with bacteremia, to distinguish between Enterobacteriaceae and other organisms.
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PMID:Antibody responses to Escherichia coli J5 lipopolysaccharide and to Salmonella porin in patients with bacteremia. 285 3

It is not clear which factors are responsible for the deficient resistance of human neonates to K1 E. coli sepsis and meningitis. To evaluate the relative importance of different defense mechanisms against bacterial invasion, we have analyzed the sensitivity of newborn mice with known immune deficiencies to infection after oral challenge with virulent K1 E. coli. T and B lymphocyte and complement (C5) defects had no significant effect on natural resistance. In contrast, both endotoxin-hyporesponsive mouse strains tested were highly sensitive. This susceptibility to infection was strongly age dependent. Infant endotoxin-hyporesponsive mice were killed by i.p. injection of less than ten virulent K1 E. coli cells. In contrast, endotoxin-responsive animals and F1 hybrids derived from crosses between endotoxin-responsive and hyporesponsive mice survived an injection with up to 10(4) bacteria. Mutants of a virulent 018:K1 E. coli strain defective in the synthesis of the capsular polysaccharide or the O-antigen of lipopolysaccharide were avirulent as were 01:K1 bacteria, which are under-represented among E. coli isolates from neonatal meningitis. Endotoxin-hyporesponsive mice were protected from lethal bacterial challenge by monoclonal IgG specific for the O-antigen of the challenge strain or by human recombinant interleukin 1. A fulminant bacterial multiplication in the bloodstream of endotoxin-hyporesponsive mice was observed after i.v. injection of 100 virulent K1 E. coli cells. Persistent bacteremia with 10(5) to 10(6) bacteria per ml of blood resulted in death of the animals one to two days after challenge. In the bloodstream of endotoxin-responsive mice the bacteria proliferated to a comparable extent within the first 6 h after challenge. Thereafter they were rapidly cleared from the circulation and the animals recovered from the infection.
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PMID:Host factors in the resistance of newborn mice to K1 Escherichia coli infection. 305 39


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