A novel post-exposure medical countermeasure L-97-1 improves survival and acute lung injury following intratracheal infection with Yersinia pestis:

Innate Immunity

Constance NWilson¹ 

关键词: Yersinia pestis;    plague;    medical countermeasure;    lipopolysaccharide;    A1 adenosine receptors;   

DOI  :  10.1177/1753425911411595

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

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 lu...

【 授权许可】

CC BY