Severe Acinetobacter baumannii Sepsis Is Associated With Elevation of Pentraxin 3
ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX
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Multidrug-resistant Acinetobacter baumannii is among the most prevalent bacterial pathogens associated with trauma-related wound and bloodstream infections. Although septic shock and disseminated intravascular coagulation have been reported following fulminant A. baumannii sepsis, little is known about the protective host immune response to this pathogen. In this study, we examined the role of PTX3, a soluble pattern recognition receptor with reported antimicrobial properties and stored within neutrophil granules. PTX3 production by murine J774a.1 macrophages was assessed following challenge with A. baumannii strains ATCC 19606 and clinical isolates CI 77, 78, 79, 80, and 86. Interestingly, only CI strains 79, 80, and 86 induced PTX3 synthesis in murine J774a.1 macrophages, with greatest production observed following CI 79 and 86 challenge. Subsequently, C57BL6 mice were challenged intraperitoneally with CI 77 and 79 to assess the role of PTX3 in vivo. A. baumannii strain CI 79 exhibited significantly P0.0005 increased mortality, with an approximate 50 lethal dose LD50 of 105 CFU, while an equivalent dose of CI 77 exhibited no mortality. Plasma leukocyte chemokines KC, MCP-1, and RANTES and myeloperoxidase activity were also significantly elevated following challenge with CI 79, indicating neutrophil recruitmentactivation associated with significant elevation in serum PTX3 levels. Furthermore, 10-fold-greater PTX3 levels were observed in mouse serum 12 h postchallenge, comparing CI 79 to CI 77 1,561 ngml versus 145 ngml, with concomitant severe pathology liver and spleen and coagulopathy. Together, these results suggest that elevation of PTX3 is associated with fulminant disease during A. baumannii sepsis.
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