Detoxification of Bacterial Lipopolysaccharides (Endotoxins) by a Human Neutrophil Enzyme

Munford, Robert S.; Hall, Christopher D.

doi:10.1126/science.3529396

Cited by 255 publications

(159 citation statements)

References 23 publications

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“…Taken together, these results imply that crayfish haemocytes are able to react differentially to the polysaccharide and lipid A moieties of LPS, where lipid A is cytotoxic and the polysaccharide portion stimulatory. This result agrees with the recognized endotoxic properties of lipid A in LPS [29,30], and the observed reduction of toxicity of deacylated LPS that still possesses potent inflammatory properties in humans [31,32]. The reaction of live haemocytes to LPS Rc, and LPSdex is similar to the reported effects of these molecules on the proPO activation from cell lysates, where LPS Rc was effective in activating the system and LPSdex was not [12].…”

Section: Discussionsupporting

confidence: 87%

Flow cytometric analysis of crayfish haemocytes activated by lipopolysaccharides

Cárdenas

Dankert

Jenkins

2004

Fish & Shellfish Immunology

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Lipopolysaccharides (LPS) from Gram-negative bacteria are strong stimulators of white river crayfish, Procambarus zonangulus, haemocytes in vitro. Following haemocyte treatment with LPS and with LPS from rough mutant R5 (LPS Rc) from Salmonella minnesota, flow cytometric analysis revealed a conspicuous and reproducible decrease in cell size as compared to control haemocytes. These LPS molecules also caused a reduction in haemocyte viability as assessed by flow cytometry with the fluorescent dyes calcein-AM and ethidium homodimer. The onset of cell size reduction was gradual and occurred prior to cell death. Haemocytes treated with LPS from S. minnesota without the Lipid A moiety (detoxified LPS) decreased in size without a reduction of viability. The action of LPS on crayfish haemocytes appeared to be related to the activation of the prophenoloxidase system because phenoloxidase (PO)-specific activity in the supernatants from control and detoxified LPS-treated cells was significantly lower than that from LPS and LPS-Rc treated cells (P % 0:05). Furthermore, addition of trypsin inhibitor to the LPS treatments caused noticeable delays in cell size and viability changes. These patterns of cellular activation by LPS formulations indicated that crayfish haemocytes react differently to the polysaccharide and lipid A moieties of LPS, where lipid A is cytotoxic and the polysaccharide portion is stimulatory. These effects concur with the general pattern of mammalian cell activation by LPS, thereby indicating common innate immune recognition mechanisms to bacterial antigens between cells from mammals and invertebrates. These definitive molecular approaches used to verify and identify mechanisms of invertebrate haemocyte responses to LPS could be applied with other glycoconjugates, soluble mediators, or xenobiotic compounds.

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Section: Discussionsupporting

confidence: 87%

Flow cytometric analysis of crayfish haemocytes activated by lipopolysaccharides

Cárdenas

Dankert

Jenkins

2004

Fish & Shellfish Immunology

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“…During multiplication, destruction and lysis, they release an outer-membrane component, the endotoxin or LPS [68], a thermostable molecule that is a unique structural component of the cell wall of the Gram-negative pathogens. Two phenotypic forms of coliforms with slightly different LPS can be distinguished: smooth with complete LPS sidechains and rough with incomplete LPS side-chains [65,154,169]. Many studies have shown that the pathogenicity of E. coli in the mammary gland is associated with LPS.…”

Section: Endotoxin As Local Mediatormentioning

confidence: 99%

“…A significant detoxification system is acyloxyacyl hydrolase (AOAH), which is present in bovine neutrophil granules [154]. AOAH hydrolyses two acyl chains of the lipid A core of the endotoxin, resulting in a decreased toxicity whereas the immunogenic properties of LPS are largely maintained [169]. In some cows, a decreased blood neutrophil AOAH activity was observed immediately after calving [60].…”

Section: Endotoxin Clearancementioning

confidence: 99%

Severity of E. coli mastitis is mainly determined by cow factors

et al. 2003

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-Intramammary infections of dairy cows with Gram-positive bacteria such as Staphylococcus aureus (major cause of mastitis) have received a lot of attention because of their major economic impact on the dairy farm through production losses induced by an increase in somatic cell count. Management strategies, including greater awareness for efficient milking and hygienic measures, have limited the spread of Gram-positive bacteria and resulted in a significant decrease of proportion of S. aureus isolates and subclinical mastitis worldwide. Other organisms such as coliform subspecies and Streptococcus uberis, both environmental bacteria that cause clinical mastitis, have received less attention. Escherichia coli causes inflammation of the mammary gland in dairy cows around parturition and during early lactation with striking local and sometimes severe systemic clinical symptoms. This disease affects many high producing cows in dairy herds and may cause several cases of death per year in the most severe cases. It is well known that bacterial, cow and environmental factors are interdependent and influence mastitis susceptibility. Many studies, executed during the last decade, indicate that the severity of E. coli mastitis is mainly determined by cow factors rather than by E. coli pathogenicity. During E. coli mastitis, the host defense status is a cardinal factor determining the outcome of the disease. Today, we know that the neutrophil is a key factor in the cows' defense against intramammary infection with E. coli. Effective elimination of the pathogen by neutrophils is important for the resolution of infection and the outcome of E. coli mastitis. This review is a compilation of some major findings over the last 15 years concerning mainly host factors that modulate and influence neutrophil function and the mammary inflammatory reaction. The individual chapters address: virulence factors of E. coli strains, how neutrophils kill E. coli, connection between endotoxins, tumor necrosis factor-a and nitric oxide, severity classification of E. coli mastitis, lifespan of neutrophils, host factors that influence severity, tissue damage and production loss.

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“…During the saponification, any LPS or lipopeptide would be inactivated because saturated fatty acids acylated in lipid A or lipopeptides will be hydrolyzed. It is well documented that if fatty acids acylated in LPS or lipopeptides are removed, their endotoxic activity is abolished (25)(26)(27). Any LPS or lipopeptide would also be eliminated during the vacuum distillation of fatty acids.…”

Section: Figurementioning

confidence: 99%

Saturated and Polyunsaturated Fatty Acids Reciprocally Modulate Dendritic Cell Functions Mediated through TLR4

Weatherill

Lee

Zhao

et al. 2005

The Journal of Immunology

273

204

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TLRs provide critical signals to induce innate immune responses in APCs such as dendritic cells (DCs) that in turn link to adaptive immune responses. Results from our previous studies demonstrated that saturated fatty acids activate TLRs, whereas n-3 polyunsaturated fatty acids inhibit agonist-induced TLR activation. These results raise a significant question as to whether fatty acids differentially modulate immune responses mediated through TLR activation. The results presented in this study demonstrate that the saturated fatty acid, lauric acid, up-regulates the expression of costimulatory molecules (CD40, CD80, and CD86), MHC class II, and cytokines (IL-12p70 and IL-6) in bone marrow-derived DCs. The dominant negative mutant of TLR4 or its downstream signaling components inhibits lauric acid-induced expression of a CD86 promoter-reporter gene. In contrast, an n-3 polyunsaturated fatty acid, docosahexaenoic acid, inhibits TLR4 agonist (LPS)-induced up-regulation of the costimulatory molecules, MHC class II, and cytokine production. Similarly, DCs treated with lauric acid show increased T cell activation capacity, whereas docosahexaenoic acid inhibits T cell activation induced by LPS-treated DCs. Together, our results demonstrate that the reciprocal modulation of both innate and adaptive immune responses by saturated fatty acid and n-3 polyunsaturated fatty acid is mediated at least in part through TLRs. These results imply that TLRs are involved in sterile inflammation and immune responses induced by nonmicrobial endogenous molecules. These results shed new light in understanding how types of dietary fatty acids differentially modulate immune responses that could alter the risk of many chronic diseases.

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Detoxification of Bacterial Lipopolysaccharides (Endotoxins) by a Human Neutrophil Enzyme

Cited by 255 publications

References 23 publications

Flow cytometric analysis of crayfish haemocytes activated by lipopolysaccharides

Flow cytometric analysis of crayfish haemocytes activated by lipopolysaccharides

Severity of E. coli mastitis is mainly determined by cow factors

Saturated and Polyunsaturated Fatty Acids Reciprocally Modulate Dendritic Cell Functions Mediated through TLR4

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