Lipoteichoic Acid from Viridans Streptococci Induces the Production of Tumor Necrosis Factor and Nitric Oxide by Murine Macrophages

English, B. Keith; Patrick, Christian C.; Orlicek, Shari L.; McCordic, Ross; Shenep, Jerry L.

doi:10.1093/infdis/174.6.1348

Cited by 41 publications

(26 citation statements)

References 12 publications

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“…Nevertheless, all of these studies support the notion that contaminating endotoxin in commercially available LTA preparations can and does contribute significantly to the observed biological activity of LTA, even though the role of pure LTA alone in inflammatory cell activation cannot be overlooked. Also worthy of note is a recent report by English et al (8). In those studies, commercially available LTA from gram-positive bacteria S. sanguis and Streptococcus mutans were shown to induce TNF-␣ and NO production from RAW 264.7 macrophages.…”

Section: Discussionmentioning

confidence: 90%

Commercial Preparations of Lipoteichoic Acid Contain Endotoxin That Contributes to Activation of Mouse Macrophages In Vitro

et al. 2001

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Lipoteichoic acids (LTA), cell wall components of gram-positive bacteria, have been reported to induce various inflammatory mediators and to play a key role in gram-positive-microbe-mediated septic shock. In a large number of these studies, investigators used commercially available LTA purified from a variety of gram-positive bacteria, including Staphylococcus aureus, Bacillus subtilis, and Streptococcus sanguis. We report here that, although these commercially available LTA could be readily shown to stimulate production of nitric oxide (NO) in RAW 264.7 mouse macrophages, the activity was dramatically inhibited by polymyxin B, a relatively specific inhibitor of endotoxin biological activity. One-step purification of the commercially available S. aureus LTA using hydrophobic interaction chromatography resulted in two well-separated peak fractions, one highly enriched for LTA and a second highly enriched for endotoxin. The LTA-enriched fractions did not induce production of NO in RAW 264.7 macrophages, although they caused a dose-dependent induction of NO in the presence of low concentrations of gamma interferon (IFN-␥) (which by itself induced little NO), regardless of the presence of polymyxin B. In contrast, the endotoxin-enriched fractions by themselves inhibited in high levels of NO in RAW 264.7 macrophages but activity was almost completely inhibited in the presence of polymyxin B. Consistent with these findings, our data also indicate that commercial LTA preparations from S. aureus, B. subtilis, and S. sanguis were not able to induce NO from lipopolysaccharidehyporesponsive C3H/HeJ mouse peritoneal macrophages, but in the presence of IFN-␥, these LTA preparations were able to induce relatively high levels of NO from C3H/HeJ macrophages. These results indicate that commercially available LTA can contain contaminating and potentially significant levels of endotoxin that can be expected to contribute to the putative macrophage-stimulating effects of LTA as assessed by NO production. The fact that the purified LTA, by itself, was not able to induce significant levels of NO secretion in RAW 264.7 macrophages supports the conclusion that caution in attributing high-level biological activity to this microbial cell wall constituent should be exercised.

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Section: Discussionmentioning

confidence: 90%

Commercial Preparations of Lipoteichoic Acid Contain Endotoxin That Contributes to Activation of Mouse Macrophages In Vitro

et al. 2001

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“…The host inflammatory response to bacteria is triggered by bacterial products including Gram-negative bacterial endotoxin or LPS, Gram-positive bacterial lipopeptides, bacterial exotoxins, hemolysins, and bacterial DNA (11)(12)(13)(14)(15)(16). Some of these bacterial products are secreted (e.g.…”

mentioning

confidence: 99%

Group B Streptococci Exposed to Rifampin or Clindamycin (versus Ampicillin or Cefotaxime) Stimulate Reduced Production of Inflammatory Mediators by Murine Macrophages

Brinkmann

Talati

Akbari³

et al. 2005

Pediatr Res

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“…Macrophage activation by C 2 -and C 6 -ceramide was not due to contaminating endotoxin Polymyxin B binds to LPS and potently blocks LPS-mediated macrophage activation and inflammatory mediator production [12,16,17]. We found that concentrations of polymyxin B sufficient to block LPS-mediated TNF and iNOS production by RAW 264.7 macrophages had no effect on the ability of either ceramide analog to trigger TNF secretion (Fig.…”

Section: Murine Macrophagesmentioning

confidence: 66%

“…As with many other stimuli [16,21], co-stimulation with low concentrations of rIFN-␥ is necessary for ceramide-induced stimulation of iNOS protein accumulation by these cells. It is interesting that a recent study found that ceramide analogs alone failed to induce iNOS accumulation or NO production in rat primary astrocytes, but that these ceramide analogs greatly augmented the ability of LPS to up-regulate iNOS and NO in these cells [7].…”

Section: Discussionmentioning

confidence: 97%

Ceramide-mediated stimulation of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF) accumulation in murine macrophages requires tyrosine kinase activity

Knapp

English

2000

Journal of Leukocyte Biology

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In macrophages, bacterial lipopolysaccharide (LPS) has been noted to mimic certain effects of the sphingolipid ceramide, suggesting that ceramide may be involved in macrophage activation by LPS and/or that LPS utilizes ceramiderelated signaling pathways. Putative downstream targets of ceramide include a ceramide-activated (serine/threonine) protein kinase (CAPK) and phosphatase (CAPP). However, the potential role of tyrosine phosphorylation pathways in macrophage response to ceramide has not been examined. Herein we report that cell-permeable analogs of ceramide up-regulate both inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF) production in RAW 264.7 murine macrophages. Herbimycin A and genistein, potent natural inhibitors of protein tyrosine (but not serine/threonine) phosphorylation, block ceramide-induced iNOS and TNF production. Furthermore, the highly srcfamily selective pyrazolopyrimidine inhibitor PP1 also blocks ceramide-induced iNOS and TNF production in RAW 264.7 cells. We found that PP1 also inhibits ceramide-mediated tyrosine phosphorylation of the src-family kinase hck. These data indicate that src-related tyrosine kinases play a critical role in macrophage activation by ceramide.

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Lipoteichoic Acid from Viridans Streptococci Induces the Production of Tumor Necrosis Factor and Nitric Oxide by Murine Macrophages

Cited by 41 publications

References 12 publications

Commercial Preparations of Lipoteichoic Acid Contain Endotoxin That Contributes to Activation of Mouse Macrophages In Vitro

Commercial Preparations of Lipoteichoic Acid Contain Endotoxin That Contributes to Activation of Mouse Macrophages In Vitro

Group B Streptococci Exposed to Rifampin or Clindamycin (versus Ampicillin or Cefotaxime) Stimulate Reduced Production of Inflammatory Mediators by Murine Macrophages

Ceramide-mediated stimulation of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF) accumulation in murine macrophages requires tyrosine kinase activity

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