Neutrophil and monocyte toll-like receptor 4, CD11b and reactive oxygen intermediates, and neuroimaging outcomes in preterm infants

Pediatr Res. 2015 Jul;78(1):82-90. doi: 10.1038/pr.2015.66. Epub 2015 Mar 31.

Abstract

Background: Activated leukocytes and infection are implicated in neonatal brain injury. Leukocyte surface receptors are increased in stroke models and may be targets for future adjunctive therapies.

Methods: Serial blood samples were analyzed from preterm infants (n = 51; <32 wk gestation) on days 0, 1, 2, and 7 of life. Monocyte and neutrophil activation were evaluated via flow cytometry at baseline and following endotoxin stimulation ex vivo by measuring CD11b (activation), toll-like receptor 4 (TLR-4; endotoxin recognition) expression, and intracellular reactive oxygen intermediate (ROI) production (function).

Results: Control preterm infants with normal neuroimaging had elevated baseline CD11b and TLR-4 expression and ROI production compared with adults as well as a robust immune response following endotoxin stimulation. Preterm infants with abnormal neuroimaging had increased neutrophil TLR-4 and ROI compared with all controls.

Conclusion: Preterm infants have a robust immune response compared with adults. Increased TLR-4 expression in preterm infants with abnormal neuroimaging is similar to findings in adult stroke. In addition, ROI production may cause tissue injury. The modulation of these responses may be beneficial in preterm inflammatory disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain Injuries / blood*
  • CD11b Antigen / blood*
  • Cell Membrane / metabolism
  • Female
  • Flow Cytometry
  • Gene Expression Regulation
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Lipopolysaccharides / chemistry
  • Magnetic Resonance Imaging
  • Male
  • Monocytes / cytology*
  • Neuroimaging
  • Neutrophils / cytology*
  • Oxygen / metabolism
  • Reactive Oxygen Species / metabolism*
  • Toll-Like Receptor 4 / blood*

Substances

  • CD11b Antigen
  • ITGAM protein, human
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Oxygen