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.
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461.
Johanna
J
Rivera
Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine, Bronx, New York 10461.
Rani S
RS
Sellers
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461.
Wangyong
W
Zeng
Department of Molecular Cell Biology, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands.
Nico
N
van Rooijen
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461; Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine, Bronx, New York 10461.
Arturo
A
Casadevall
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461; Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461. Electronic address: david.goldman@einstein.yu.edu.
David L
DL
Goldman
D000818:Animals; D000881:Anthrax / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000942:Antigens, Bacterial / Q000378:metabolism*; D001408:Bacillus anthracis / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D008168:Lung / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D010972:Platelet Activating Factor / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism / Q000473:pathology
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018925:Chemokines; D016207:Cytokines; D010972:Platelet Activating Factor; C030325:anthrax toxin
Anthrax Toxin; Bacterial Pathogenesis; Cytokine; Lipids; Macrophages; Platelet-activating Factor