A novel post-exposure medical countermeasure L-97-1 improves survival and acute lung injury following intratracheal infection with Yersinia pestis
| Autor: | Constance O. Vance, David S. Brink, Timothy M. Doyle, Andrew J. Lechner, Constance N. Wilson, George M. Matuschak |
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| Rok vydání: | 2011 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide Virulence Factors Yersinia pestis Acute Lung Injury Immunology Lung injury Microbiology Article Virulence factor chemistry.chemical_compound Ciprofloxacin Animals Humans Medicine Lung Molecular Biology Pathogen Plague biology Receptor Adenosine A1 business.industry Antagonist Cell Biology biology.organism_classification Rats Disease Models Animal Infectious Diseases medicine.anatomical_structure chemistry Purines Drug Therapy Combination business Protein Binding medicine.drug |
| Zdroj: | Innate Immunity. 18:373-389 |
| ISSN: | 1753-4267 1753-4259 |
| DOI: | 10.1177/1753425911411595 |
| Popis: | Yersinia pestis, a Gram-negative bacillus causing plague and Centers for Disease Control and Prevention (CDC) classified Category A pathogen, has high potential as a bioweapon. Lipopolysaccharide, a virulence factor for Y. pestis, binds to and activates A1 adenosine receptor (AR)s and, in animals, A1AR antagonists block induced acute lung injury (ALI) and increase survival following cecal ligation and perforation. In this study, rats were infected intratracheally with viable Y. pestis [CO99 (pCD1+/Δpgm) 1 × 108 CFU/animal] and treated daily for 3 d with ciprofloxacin (cipro), the A1AR antagonist L-97-1, or cipro plus L-97-1 starting at 0, 6, 24, 48, or 72 h post- Y. pestis. At 72 h post- Y. pestis, cipro plus L-97-1 significantly improved 6-d survival to 60–70% vs 28% for cipro plus H2O and 33% for untreated Y. pestis controls ( P = 0.02, logrank test). Lung edema, hemorrhage and leukocyte infiltration index (LII) were evaluated histologically to produce ALI scores. Cipro plus L-97-1 significantly reduced lung edema, as well as aggregate lung injury scores vs controls or cipro plus H2O, and LII vs controls ( P |
| Databáze: | OpenAIRE |
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