Innate immune activation in neonatal tracheal aspirates suggests endotoxin-driven inflammation
| Autor: | Katheryn Nathe, Linda J. Van Marter, Liat Stoler-Barak, Victoria J. Philbin, Christine D. Palmer, Richard B. Parad, Michele Phillips, Christy J. Mancuso, Ofer Levy, Camilia R. Martin |
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| Rok vydání: | 2012 |
| Předmět: |
animal structures
animal diseases chemical and pharmacologic phenomena Inflammation Biology Real-Time Polymerase Chain Reaction 03 medical and health sciences 0302 clinical medicine 030225 pediatrics medicine Humans Clinical Investigation Limulus Test Analysis of Variance Innate immune system S100 Proteins S100A12 Protein Age Factors Infant Newborn biochemical phenomena metabolism and nutrition respiratory system Flow Cytometry Respiration Artificial Immunity Innate 3. Good health Endotoxins Trachea Microscopy Fluorescence Pediatrics Perinatology and Child Health Immunology Cytokines bacteria medicine.symptom 030215 immunology |
| Zdroj: | Pediatric Research |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1038/pr.2012.61 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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