Innate immune activation in neonatal tracheal aspirates suggests endotoxin-driven inflammation.
Pediatr Res
; 72(2): 203-11, 2012 Aug.
Article
em En
| MEDLINE
| ID: mdl-22580716
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-1ß 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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Respiração Artificial
/
Traqueia
/
Recém-Nascido
/
Proteínas S100
/
Endotoxinas
/
Imunidade Inata
Limite:
Humans
Idioma:
En
Revista:
Pediatr Res
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos