Innate immune activation in neonatal tracheal aspirates suggests endotoxin-driven inflammation
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Innate immune activation in neonatal tracheal aspirates suggests endotoxin-driven inflammation
| Title: | Innate immune activation in neonatal tracheal aspirates suggests endotoxin-driven inflammation |
| Author: |
Mancuso, Christy J.; Stoler-Barak, Liat; Philbin, Victoria J.; Phillips, Michele F.; Palmer, Christine D.; Nathe, Katheryn; Parad, Richard Barry; Van Marter, Linda Joanne; Martin, Camilia Rivera; Levy, Ofer
Note: Order does not necessarily reflect citation order of authors. |
| Citation: | Nathe, Katheryn E., Christy J. Mancuso, Richard Parad, Linda J. Van Marter, Camilia R. Martin, Liat Stoler-Barak, Victoria J. Philbin, Michele F. Phillips, Christine D. Palmer, and Ofer Levy. 2012. Innate immune activation in neonatal tracheal aspirates suggests endotoxin-driven inflammation. Pediatric Research 72(2): 203-211. |
| Full Text & Related Files: |
3406551.pdf (796.8Kb; PDF) 
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| Abstract: | Background:: Tracheal aspirates (TAs) from critically ill neonates accumulate bacterial endotoxin and demonstrate mobilization of endotoxin-binding proteins, but the potential bioactivity of endotoxin in TAs is unknown. We characterized innate immune activation in TAs of mechanically ventilated neonates. Methods: Innate immune activation in TAs of mechanically ventilated neonates was characterized using a targeted 84-gene quantitative real-time (qRT) PCR array. Protein expression of cytokines was confirmed by multiplex assay. Expression and localization of the endotoxin-inducible antimicrobial protein Calgranulin C (S100A12) was assessed by flow cytometry. Endotoxin levels were measured in TA supernatants using the Limulus amoebocyte lysate assay. Results:: Analyses by qRT-PCR demonstrated expression of pattern recognition receptors, Toll-like receptor-nuclear factor κB and inflammasome pathways, cytokines/chemokines and their receptors, and anti-infective proteins in TA cells. Endotoxin positivity increased with postnatal age. As compared with endotoxin-negative TAs, endotoxin-positive TAs demonstrated significantly greater tumor necrosis factor (TNF), interleukin (IL)-6, IL-10, and serpin peptidase inhibitor, clade E, member 1 (SERPINE1) mRNA, and IL-10, TNF, and IL-1β protein. Expression of S100A12 protein was localized to TA neutrophils. Conclusion:: Correlation of endotoxin with TA inflammatory responses suggests endotoxin bioactivity and the possibility that endotoxin antagonists could mitigate pulmonary inflammation and its sequelae in this vulnerable population. |
| Published Version: | doi:10.1038/pr.2012.61 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406551/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:10436299 |
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