Platelet-activating Factor Contributes to Bacillus anthracis Lethal Toxin-associated Damage |
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| Authors: | Johanna Rivera Rani S Sellers Wangyong Zeng Nico van Rooijen Arturo Casadevall David L Goldman |
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| Institution: | From the Departments of ‡Microbiology and Immunology.;§Medicine (Division of Infectious Diseases).;¶Pathology, and ;**Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461 and ;the ‖Department of Molecular Cell Biology, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands |
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| Abstract: | 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. |
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| Keywords: | Anthrax Toxin Bacterial Pathogenesis Cytokine Lipids Macrophages Platelet-activating Factor |
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