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

Previous experimental and clinical studies have demonstrated the ability of polyclonal antibody directed against the core lipopolysaccharide (LPS)-lipid A component of endotoxin to reduce mortality. We sought to characterize the ability of a single murine monoclonal IgG1 antibody (8A1 MAb) to react to a variety of gram-negative microorganisms, to promote phagocytosis, and to provide protection during experimental murine sepsis. The 8A1 MAb reacted to various gram-negative bacterial whole cell and LPS antigens examined by enzyme-linked immunosorbent assay. Reactivity was highest to Salmonella minnesota Re LPS and lipid A. Phagocytosis was promoted by this monoclonal antibody to several gram-negative bacteria, except Pseudomonas aeruginosa. The 8A1 MAb (2 mg per mouse) enhanced survival during bacteremia due to either Escherichia coli 0111:B4 or Klebsiella pneumoniae, and during endotoxemia due to all types of LPS examined except P aeruginosa. We concluded that a single MAb with anti-lipid A specificity was cross reactive in vitro and cross protective in vivo. A clinical trial comparing polyclonal and monoclonal antibody in high-risk septic patients seems warranted.
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PMID:Immunotherapy of gram-negative bacterial sepsis. A single murine monoclonal antibody provides cross-genera protection. 394

Vaccination with heat-killed or formalinized cells of E coli 0:111, or E coli 06 (Williams), prevented retrograde E coli pyelonephritis. Since there was no bacteremia and no urinary antibody, the vaccination appeared to protect by immune reactions operating in the kidney itself. The vaccine failed to protect against a highly virulent form of E coli 06 (Riffle), possibly because the amount of antibody to its lipopolysaccharide was inadequate. Since all three strains possessed K antigen in approximately equal amounts, the difference in results was not attributed to its presence.
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PMID:Immunization against retrograde pyelonephritis. II. Prevention of retrograde Escherichia coli pyelonephritis with vaccines. 459 Jun 46

By crossed immunoelectrophoresis 36 different anode-migrating antigens were demonstrated in sonicated antigen preparations of Pseudomonas aeruginosa. We numbered these antigens to establish a reference precipitin pattern. Antigen no. 31 was identified as the lipopolysaccharide (LPS) antigen, because it was found to be responsible for the O-group specificity and because it reacted with anti-LPS monoclonal antibodies and with Limulus amoebocyte lysate. Purified outer membrane proteins F (porin), H2, and I used as antigens formed precipitins with the reference antibodies, thus establishing their antigenicity. LPS that copurified with protein F and slightly contaminated protein H2 was detectable as an extra precipitin (antigen no. 31). The use of monoclonal antibodies specific for smooth LPS and rough LPS revealed different antigenic determinants in the LPS molecule and suggested that antigen no. 5 could be the core region of the LPS which is equivalent to the rough LPS. Antibodies against these outer membrane antigens were detected in patients with chronic P. aeruginosa pneumonia and in patients with acute P. aeruginosa bacteremia. Antibodies with the same specificity were also found in rats chronically infected with P. aeruginosa 7 days postinfection. This demonstrates the surface accessibility and antigenic reactivity of outer membrane antigens.
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PMID:Immunogenicity of Pseudomonas aeruginosa outer membrane antigens examined by crossed immunoelectrophoresis. 619 19

Epidemiological data show that O18:K1 Escherichia coli is a common cause of neonatal bacteremia and meningitis. These bacteria were capable of multiplying in the bloodstream of newborn rats and were resistant to the bactericidal effects of complement in the absence of specific antibodies. The roles played by the O antigen and the K antigen in complement resistance were analyzed by comparing the bactericidal effects of normal sera and of sera deficient in various complement components or in immunoglobulins. These sera were tested on O18:K1 bacteria and on mutants lacking either the lipopolysaccharide O antigen or the K1 capsular polysaccharide. In addition, O1:K1 cells, which can cause pyelonephritis but which are rare in newborn meningitis and which do not multiply in the bloodstream of newborn rats, were also examined. Different mechanisms of protection against the alternative and classical pathways were recognized: K1-positive cells were resistant to the bactericidal activity of sera deficient in classical complement pathway components, whereas K1-negative cells were sensitive to these sera. Based on these results and on those from complement fixation assays, the K1 sialic acid polysaccharide impedes the activation of, and thus protects the bacteria against, the alternative complement pathway. Not only the K1-negative mutant cells but also O1:K1 bacteria and mutants lacking the O18 oligosaccharide repeating units of the lipopolysaccharide were sensitive to the classical complement pathway. These bactericidal effects were observed even in the absence of specific antibodies. It is proposed that both the K1 capsule and the O18 oligosaccharide restrict antibody-independent classical pathway activation by shielding deeper structures on the cell membrane that are capable of activating this pathway.
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PMID:Role of the capsule and the O antigen in resistance of O18:K1 Escherichia coli to complement-mediated killing. 619 96

A total of 95 K1 Escherichia coli strains of the O (lipopolysaccharide) serotypes O1, O7, or O18 had been analyzed previously for the ability to cause bacteremia after colonizing the gut of newborn rats. In this study, these strains were tested for their resistance to the bactericidal activity of rat serum. All strains that had caused bacteremia in a high percentage of the inoculated rats were able to survive for several hours in 90% adult rat serum. With only a few exceptions, O7:K1 and O18:K1 strains were serum resistant and virulent, whereas O1:K1 strains were serum sensitive and avirulent. Serum sensitivity was due to the classical complement pathway. K1 strains of all three O serotypes were resistant to the alternative complement pathway. O7:K1 and O18:K1 cells were killed efficiently after the classical pathway was triggered by specific antilipopolysaccharide antibodies. However, killing of O1:K1 bacteria by the classical pathway system did not require antibodies. Isolated O1-lipopolysaccharide fixed complement more efficiently than did isolated O7- or O18-lipopolysaccharide, suggesting that the differences in the chemical structure of the O antigens are responsible for the observed differences in complement sensitivity. In combination with epidemiological data, the results indicate that antibody-independent classical pathway activation provides an important defense mechanism for newborns against certain gram-negative infections.
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PMID:Degree of antibody-independent activation of the classical complement pathway by K1 Escherichia coli differs with O antigen type and correlates with virulence of meningitis in newborns. 619 83

The ability of antisera against lipopolysaccharide (LPS) raised by immunization with gram-negative bacteria to prevent LPS toxicity and death from gram-negative bacteremia is well established. To demonstrate conclusively that the protective antibody is specific for LPS, we tested an anti-LPS monoclonal antibody (mAb) in three animal models. 7G is an IgG3 mAb directed against an oligosaccharide side chain determinant of LPS from E. coli 0111:B4. This anti-LPS mAb increased the LD50 of 0111:B4 LPS in mice and protected rabbits against the dermal Shwartzman reaction elicited by 0111:B4 LPS. 7G mAb also protected mice against lethal infection with mucin-enhanced E. coli 0111:B4. Pretreatment with 250 micrograms of 7G increased the LD50 by more than 1.5 logs. These studies prove that oligosaccharide side chain-specific antibody to LPS confers protection against LPS toxicity in vivo and against experimental gram-negative infection. In addition, these studies suggest the potential of anti-LPS monoclonal antibody as therapy for gram-negative infection.
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PMID:An immunoprotective monoclonal antibody to lipopolysaccharide. 620 51

We describe two mouse monoclonal antibodies reactive with lipopolysaccharide derived from the J5 mutant of Escherichia coli O111:B4. These antibodies react with purified lipopolysaccharide derived from rough mutants of E. coli and Salmonella typhimurium and also with lipopolysaccharide associated with both smooth- and rough-phenotype, gram-negative bacteria. Both antibodies appear to bind determinants present in the lipopolysaccharide core region, and this reactivity is inhibited in the presence of polymyxin B. Although their patterns of reactivity differ, both antibodies exhibit extensive serological cross-reactivity with a variety of gram-negative bacteria. Reagents of this type should prove useful in animal models to delineate the requisite affinity, epitope specificity, immunoglobulin class, etc., needed for the prevention and treatment of gram-negative bacteremia.
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PMID:Mouse monoclonal antibodies reactive with J5 lipopolysaccharide exhibit extensive serological cross-reactivity with a variety of gram-negative bacteria. 620 22

Gram-negative bacterial sepsis and shock remain a cause of substantial morbidity and mortality in hospitalized patients despite appropriate antimicrobial therapy, fluid resuscitation, and monitoring. We sought to test the ability of equine antibody directed against core endotoxin, a portion of bacterial outer membrane lipopolysaccharide common to many gram-negative microorganisms, to bind to various gram-negative bacteria in vitro, to promote bacterial phagocytosis by leukocytes, and to protect against lethal gram-negative bacteremia in mice. The importance of the IgG Fc leukocyte attachment site was examined by comparing the ability of intact IgG and IgG F(ab')2 fragments to protect against lethality during murine sepsis. A single horse was immunized with Escherichia coli J5, an organism that expresses a portion of core endotoxin extensively on the cell surface. Preimmunization IgG and F(ab')2 possessed no titer as determined by enzyme-linked immunosorbent assay, did not promote in vitro phagocytosis, and did not protect in vivo. Postimmunization IgG and F(ab')2 possessed a significant titer to E. coli J5 whole cell and lipopolysaccharide antigens and provided significant (p less than 0.05) protection in vivo during lethal intravenous sepsis caused by either E. coli J5, E. coli 0111:B4, Klebsiella pneumoniae, or Pseudomonas aeruginosa. Only postimmunization IgG, but not F(ab')2, promoted in vitro phagocytosis of these same organisms. We therefore hypothesized that protection occurred as a result of antitoxin activity rather than opsonization and phagocytosis, as F(ab')2 fragments were as active as the intact molecule. Further studies must be done to determine the role of anticore endotoxin antibody in conjunction with antibiotics so that appropriate clinical studies may be undertaken.
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PMID:Anticore endotoxin F(ab')2 equine immunoglobulin fragments protect against lethal effects of gram-negative bacterial sepsis. 637 63

The protective capacity of passively transferred immunoglobulin G (IgG) fractions from antitoxin (AT-IgG), antielastase (AE-IgG), and antilipopolysaccharide (ALPS-IgG) against Pseudomonas aeruginosa infection was evaluated in a murine burn wound sepsis model. Complete protection was afforded by homologous ALPS-IgG against intermediate challenge doses (10 50% lethal doses) of P. aeruginosa PA220, whereas AT-IgG and AE-IgG offered no significant protection (P less than 0.5). The simultaneous transfer of AT-IgG or AE-IgG with ALPS-IgG gave no additional protection above that seen with ALPS-IgG alone. The transfer of ALPS-IgG did not dramatically alter bacterial multiplication in the skin at the site of infection. However, bacteremia and infection of the liver were prevented. In parallel experiments, AT-IgG or AE-IgG did not significantly alter either the course of the infection or the number of bacteria seen in the blood, liver, or skin when compared with controls. ALPS-IgG administered 24 h before infection, at the time of infection, or 4 h postinfection provided complete protection. Even when ALPS-IgG was transferred at a time when the infection was well established locally in the skin (8 h postinfection), highly significant protection (P greater than 0.999) was obtained. Protection afforded by ALPS-IgG was serotype specific. These results indicate that antibody to lipopolysaccharide is of critical importance for protection against P. aeruginosa challenge in a relevant animal model.
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PMID:Protection against Pseudomonas aeruginosa infection in a murine burn wound sepsis model by passive transfer of antitoxin A, antielastase, and antilipopolysaccharide. 640 17

An experimental leukopenic mouse model was used to evaluate the protective capacities of immunoglobulin G (IgG) fractions directed against toxin A (AT-IgG), elastase (AE-IgG), and lipopolysaccharide (ALPS-IgG) against fatal Pseudomonas aeruginosa infection. Statistically significant protection, as measured by long-term survival, was observed only when mice were treated with serotype-specific ALPS-IgG. The mean lethal dose for P. aeruginosa could be increased by as much as 6,600-fold for mice given ALPS-IgG as compared to mice which received only normal rabbit IgG. ALPS-IgG afforded high levels of protection, even when administered up to 6 h postchallenge. Experiments designed to monitor the growth and spread of a locally administered challenge showed that ALPS-IgG prevented bacteremia and organ colonization, which were pronounced in control animals. The effectiveness of combined antibiotic and immune therapy was tested. Gentamicin alone or in combination with AT-IgG or AE-IgG provided no detectable protection. However, its use with ALPS-IgG afforded substantially higher levels of protection than ALPS-IgG alone.
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PMID:Passive protection against Pseudomonas aeruginosa infection in an experimental leukopenic mouse model. 655 39


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