Platelet-activating factor contributes to Bacillus anthracis lethal toxin-associated damage
The lethal toxin (LeTx) of Bacillus anthracis plays a central role in the pathogenesis of anthrax-associated shock. Platelet-activating factor (PAF) is a potent lipid mediator that has been implicated in endotoxin-associated shock. In this study, we examined the contribution of PAF to the manifestations of lethal toxin challenge in WT mice. LeTx challenge resulted in transient increase in serum PAF levels and a concurrent decrease in PAF acetylhydrolase activity. Inhibition of PAF activity using PAF antagonists or toxin challenge of PAF receptor negative mice reversed or ameliorated many of the pathologic features of LeTx-induced damage, including changes in vascular permeability, hepatic necrosis, and cellular apoptosis. In contrast, PAF inhibition had minimal effects on cytokine levels. Findings from these studies support the continued study of PAF antagonists as potential adjunctive agents in the treatment of anthrax-associated shock.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:289 |
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| Enthalten in: |
The Journal of biological chemistry - 289(2014), 10 vom: 07. März, Seite 7131-7141 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rivera, Johanna [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.06.2014 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1074/jbc.M113.524900 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM234981431 |
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| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The lethal toxin (LeTx) of Bacillus anthracis plays a central role in the pathogenesis of anthrax-associated shock. Platelet-activating factor (PAF) is a potent lipid mediator that has been implicated in endotoxin-associated shock. In this study, we examined the contribution of PAF to the manifestations of lethal toxin challenge in WT mice. LeTx challenge resulted in transient increase in serum PAF levels and a concurrent decrease in PAF acetylhydrolase activity. Inhibition of PAF activity using PAF antagonists or toxin challenge of PAF receptor negative mice reversed or ameliorated many of the pathologic features of LeTx-induced damage, including changes in vascular permeability, hepatic necrosis, and cellular apoptosis. In contrast, PAF inhibition had minimal effects on cytokine levels. Findings from these studies support the continued study of PAF antagonists as potential adjunctive agents in the treatment of anthrax-associated shock | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Anthrax Toxin | |
| 650 | 4 | |a Bacterial Pathogenesis | |
| 650 | 4 | |a Cytokine | |
| 650 | 4 | |a Lipids | |
| 650 | 4 | |a Macrophages | |
| 650 | 4 | |a Platelet-activating Factor | |
| 650 | 7 | |a Antigens, Bacterial |2 NLM | |
| 650 | 7 | |a Bacterial Toxins |2 NLM | |
| 650 | 7 | |a Chemokines |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Platelet Activating Factor |2 NLM | |
| 650 | 7 | |a anthrax toxin |2 NLM | |
| 700 | 1 | |a Sellers, Rani S |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Wangyong |e verfasserin |4 aut | |
| 700 | 1 | |a van Rooijen, Nico |e verfasserin |4 aut | |
| 700 | 1 | |a Casadevall, Arturo |e verfasserin |4 aut | |
| 700 | 1 | |a Goldman, David L |e verfasserin |4 aut | |
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