title: Neutrophil and monocyte toll-like receptor 4, CD11b and reactive oxygen intermediates, and neuroimaging outcomes in preterm infants.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1] Department of Paediatrics, National Maternity Hospital, Dublin 2, Ireland [2] University College Dublin School of Medicine and Medical Sciences, Dublin, Ireland [3] University College Dublin Conway Institute of Biomolecular and Biomedical Sciences, Dublin, Ireland [4] National Children's Research Centre, Dublin, Ireland.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: O'Hare
authors.affiliation: 1] University College Dublin School of Medicine and Medical Sciences, Dublin, Ireland [2] University College Dublin Conway Institute of Biomolecular and Biomedical Sciences, Dublin, Ireland.
authors.forename: William
authors.initials: W
authors.lastname: Watson
authors.affiliation: 1] University College Dublin School of Medicine and Medical Sciences, Dublin, Ireland [2] University College Dublin Conway Institute of Biomolecular and Biomedical Sciences, Dublin, Ireland.
authors.forename: Amanda
authors.initials: A
authors.lastname: O'Neill
authors.affiliation: 1] University College Dublin School of Medicine and Medical Sciences, Dublin, Ireland [2] University College Dublin Conway Institute of Biomolecular and Biomedical Sciences, Dublin, Ireland.
authors.forename: Tim
authors.initials: T
authors.lastname: Grant
authors.affiliation: 1] Department of Paediatrics, National Maternity Hospital, Dublin 2, Ireland [2] University College Dublin School of Medicine and Medical Sciences, Dublin, Ireland [3] University College Dublin Conway Institute of Biomolecular and Biomedical Sciences, Dublin, Ireland [4] National Children's Research Centre, Dublin, Ireland.
authors.forename: Chike
authors.initials: C
authors.lastname: Onwuneme
authors.affiliation: 1] Department of Paediatrics, National Maternity Hospital, Dublin 2, Ireland [2] Department of Radiology, Children's University Hospital, Dublin, Ireland.
authors.forename: Veronica
authors.initials: V
authors.lastname: Donoghue
authors.affiliation: Department of Pathology, National Maternity Hospital, Dublin 2, Ireland.
authors.forename: Eoghan
authors.initials: E
authors.lastname: Mooney
authors.affiliation: Department of Pathology, National Maternity Hospital, Dublin 2, Ireland.
authors.forename: Paul
authors.initials: P
authors.lastname: Downey
authors.affiliation: Department of Paediatrics, National Maternity Hospital, Dublin 2, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: Murphy
authors.affiliation: Department of Paediatrics, National Maternity Hospital, Dublin 2, Ireland.
authors.forename: Anne
authors.initials: A
authors.lastname: Twomey
authors.affiliation: 1] Department of Paediatrics, National Maternity Hospital, Dublin 2, Ireland [2] University College Dublin School of Medicine and Medical Sciences, Dublin, Ireland [3] University College Dublin Conway Institute of Biomolecular and Biomedical Sciences, Dublin, Ireland [4] Department of Neonatology, Our Lady's Children's Hospital, Dublin, Ireland [5] Department of Paediatrics, Royal College of Surgeons in Ireland, Dublin, Ireland [6] Department of Paediatrics, Trinity College Dublin, University of Dublin, Dublin, Ireland.
authors.forename: Eleanor J
authors.identifier: 0000000167982158
authors.initials: EJ
authors.lastname: Molloy
mesh_terms: D000328:Adult; D001930:Brain Injuries / Q000097:blood*; D039481:CD11b Antigen / Q000097:blood*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008070:Lipopolysaccharides / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D009000:Monocytes / Q000166:cytology*; D059906:Neuroimaging; D009504:Neutrophils / Q000166:cytology*; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000097:blood*
chemical_list: D039481:CD11b Antigen; C509295:ITGAM protein, human; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D010100:Oxygen
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