In vivo protective effect of lipopolysaccharide against Pseudomonas aeruginosa exotoxin A in mice

Zehavi‐Willner, Tova; Barnea, Ada; Pinto, Mary Beth

doi:10.1128/iai.59.5.1667-1672.1991

Cited by 5 publications

(4 citation statements)

References 22 publications

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“…In the present study, a significantly lower lethality was seen in rats stimulated with E. coli LPS than in the controls and rats stimulated with P. aeruginosa sonicate or vaccinated with E. coli LPS. The explanation is most likely that E. coli LPS accounts for increased non-specific defence mechanisms, which is in accordance with the results of other authors (42). A protection of the same magnitude was induced by vaccination with P. aeruginosa sonicate.…”

Section: Discussionsupporting

confidence: 90%

Experimental chronic Pseudomonas aeruginosa lung infection in rats

Lange

Hougen²,

Høiby

et al. 1995

APMIS

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In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis, we investigated the possibility of preventing chronic lung inflammation or decreasing the progression of the infection. We compared the lethality, pathology, bacterial clearance, and immunogenicity after stimulation of the non‐specific defence mechanisms by Escherichia coli lipopolysaccharide (LPS) or P. aeruginosa sonicate, or the acquired specific immune response by vaccination with the same bacterial antigens. One day prior to challenge with P. aeruginosa embedded in alginate beads, rats were stimulated with either E. coli LPS or P. aeruginosa sonicate. Four and two weeks prior to challenge other rats were vaccinated with either E. coli LPS or P. aeruginosa sonicate. Controls did not receive any stimulation or vaccination. The lethality after challenge was lower in rats stimulated with E. coli LPS (p= 0.02) or vaccinated with P. aeruginosa sonicate (p=0.03) as compared to controls. The histopathology of the surviving rats showed an acute inflammation dominated by polymorphonuclear leukocytes (PMNs), but the offending bacteria were not completely eliminated in any group. The increased survival was probably due to earlier recruitment of PMNs most likely mediated by either cytokines and other chemotactic factors (stimulated group) or the immune response in concert with the complement cascade (vaccinated group). The results of the present and previous vaccination studies show that it is possible to improve survival but not to prevent the chronic P. aeruginosa lung infection and inflammation caused by alginate‐embedded bacteria.

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Section: Discussionsupporting

confidence: 90%

Experimental chronic Pseudomonas aeruginosa lung infection in rats

Lange

Hougen²,

Høiby

et al. 1995

APMIS

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“…Since extracellular signaling molecules have the ability to modulate LRP levels, it is plausible that this regulatory mechanism may be a factor in determining cellular and even tissue PEA sensitivity in vivo. Indeed, the results of the present study may suggest an additional mechanism by which LPS confers enhanced resistance to PEA challenge in vivo (48). It is probable that the production of various LRP regulatory factors may be initiated in response to P. aeruginosa, thus modulating PEA cellular sensitivity during infection.…”

Section: Discussionmentioning

confidence: 64%

Enhanced Macrophage Resistance toPseudomonasExotoxin A Is Correlated with Decreased Expression of the Low-Density Lipoprotein Receptor-Related Protein

et al. 1999

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Cellular intoxification by exotoxin A of Pseudomonas aeruginosa (PEA) begins when PEA binds to its cellular receptor, the low-density lipoprotein receptor-related protein (LRP). This receptor is particularly abundant on macrophages. We hypothesize here that inducible changes in cellular expression levels of the LRP represent an important mechanism by which macrophage susceptibility to PEA is regulated by the host. We have examined the effect of lipopolysaccharide (LPS) on LRP expression and PEA sensitivity in the macrophage-like cell line HS-P. Using a [3H]leucine incorporation assay to measure inhibition of protein synthesis, we have demonstrated that HS-P macrophages are highly sensitive to PEA and that PEA toxicity is decreased by the LRP antagonist receptor-associated protein. LPS pretreatment decreases HS-P PEA sensitivity in a time- and dose-dependent manner. The dose of toxin required to inhibit protein synthesis by 50% increased from 11.3 ± 1.2 ng/ml in untreated cells to 25.7 ± 2.0 ng/ml in cells treated with LPS. In pulse experiments, involving brief exposure to saturating concentrations of PEA, [3H]leucine incorporation was more than threefold higher in cells pretreated with LPS than in untreated macrophages. These changes in HS-P PEA sensitivity following LPS treatment were consistently associated with a fivefold decrease in HS-P LRP mRNA expression as measured by Northern blot analysis and a three-and-a-half-fold decrease in HS-P LRP-specific ligand internalization as determined by activated α2-macroglobulin internalization studies. These data demonstrate for the first time that modulation of LRP levels by extracellular signaling molecules can alter cellular PEA sensitivity.

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“…Our findings are summarized in Table 1. Pretreatment with sublethal doses of LPS has been shown to exert anti-infiammatory eflects in a variety of systems [21][22][23]. The mechanisms of this effect are complex and seem to involve factors produced by the liver [22], and the pituitary/adrenal axis [25] as well as changes in numbers and migratory properties of neutrophils [26,27].…”

Section: Discussionmentioning

confidence: 99%

“…Pretreatment with sub-lethal doses of LPS can inhibit subsequent attempts to induce TNF-mediated pathology [21][22][23].…”

Section: Inhibition Of the Lsr By Pretreatment With Lpsmentioning

confidence: 99%

A model for the investigation of factors influencing haemorrhagic necrosis mediated by tumour necrosis factor in tissue sites primed with mycobacterial antigen preparations

Attiyah

Rosen

Rook

1992

Clinical and Experimental Immunology

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SUMMARYMycobacterial lesions and skin sites challenged with soluble mycobacterial antigen are very sensitive to the necrotizing effect of tumour necrosis factor (TNE). We have used a model that permits separate quantitative assessment of swelling and haemorrhage to show that when these reactions are elicited in mice that have not been deliberately immunized, pretreatment of the mice with lipopolysaccharide (LPS), or with a MoAb to CR3 which blocks emigration of myeloid cells into the tissues, will block both the swelling and the haemorrhage. On the other hand, treatment with an inhibitor of plateletactivating factor (PAE), or with misoprostol (a synthetic prostaglandin El analogue), or with cobra venom factor (CVE) which depletes complement, preferentially blocks the haemorrhagic component, while leaving the swelling relatively unaltered. As swelling occurs before the haemorrhage is seen, it is possible that these factors act at a late stage in the cascade of events leading to the tissue damage. However, LPS and CVF were able to inhibit swelling and haemorrhage in the massive reactions elicited in pre-immunized animals, whereas the PAE inhibitor had no detectable effect.

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In vivo protective effect of lipopolysaccharide against Pseudomonas aeruginosa exotoxin A in mice

Cited by 5 publications

References 22 publications

Experimental chronic Pseudomonas aeruginosa lung infection in rats

Experimental chronic Pseudomonas aeruginosa lung infection in rats

Enhanced Macrophage Resistance toPseudomonasExotoxin A Is Correlated with Decreased Expression of the Low-Density Lipoprotein Receptor-Related Protein

A model for the investigation of factors influencing haemorrhagic necrosis mediated by tumour necrosis factor in tissue sites primed with mycobacterial antigen preparations

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