PMID- 16508260 OWN - NLM STAT- MEDLINE DCOM- 20060911 LR - 20220310 IS - 0006-3126 (Print) IS - 0006-3126 (Linking) VI - 90 IP - 1 DP - 2006 TI - Effects of heat shock and hypoxia on neonatal neutrophil lipopolysaccharide responses: altered apoptosis, Toll-like receptor-4 and CD11b expression compared with adults. PG - 34-9 AB - BACKGROUND: Dysfunctional inflammatory responses have been implicated in several neonatal inflammatory disorders following infection and hypoxia. OBJECTIVES: We aimed to study the effects of in vitro hypoxia and heat shock (HS) on normal adult and newborn neutrophil migration (CD11b) and persistence (apoptosis) following lipopolysaccharide (LPS) stimulation. METHODS: The mechanism for altered LPS responses was assessed at the level of the LPS signalling receptors, Toll-like receptor-4 (TLR-4), TLR-2 and CD14 expression in normal neonates and adults. RESULTS: In adults, although hypoxia delayed neutrophil apoptosis, LPS enhanced this response. In contrast, HS (42 degrees C) increased adult apoptotic rates and abrogated the LPS responses. Both hypoxia and HS prevented the LPS-induced increase in adult CD11b although it was unaltered in neonates. Adult TLR-4 neutrophil expression was increased by LPS and hypoxia, and decreased in HS, possibly explaining their variable LPS responsiveness. In contrast, neonatal neutrophils were LPS hyporesponsive which may be mediated by failure of TLR-4 upregulation with LPS. CONCLUSIONS: Neonates do not have increased LPS responsiveness in hypoxia or heat shock in vitro, which may prevent hyperinflammation and thereby minimise tissue damage in inflammation or infection. CI - Copyright 2006 S. Karger AG, Basel. FAU - Molloy, Eleanor J AU - Molloy EJ AD - Department of Surgery, Conway Institute of Biomolecular and Biomedical Research, Mater Misericordiae University Hospital, Dublin, Ireland. elesean@hotmail.com FAU - O'Neill, Amanda J AU - O'Neill AJ FAU - Doyle, Belinda T AU - Doyle BT FAU - Grantham, Julie J AU - Grantham JJ FAU - Taylor, Cormac T AU - Taylor CT FAU - Sheridan-Pereira, Margaret AU - Sheridan-Pereira M FAU - Fitzpatrick, John M AU - Fitzpatrick JM FAU - Webb, David W AU - Webb DW FAU - Watson, R William G AU - Watson RW LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060223 PL - Switzerland TA - Biol Neonate JT - Biology of the neonate JID - 0247551 RN - 0 (CD11b Antigen) RN - 0 (Lipopolysaccharides) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) SB - IM MH - Adult MH - Aging/physiology MH - Apoptosis/drug effects MH - CD11b Antigen/*genetics MH - Cell Hypoxia MH - Female MH - Fetal Blood/cytology MH - Gestational Age MH - Hot Temperature MH - Humans MH - Infant, Newborn MH - Lipopolysaccharides/*pharmacology MH - Male MH - Neutrophils/*cytology/drug effects/*physiology MH - Toll-Like Receptor 4/*genetics EDAT- 2006/03/02 09:00 MHDA- 2006/09/12 09:00 CRDT- 2006/03/02 09:00 PHST- 2005/05/04 00:00 [received] PHST- 2005/10/11 00:00 [accepted] PHST- 2006/03/02 09:00 [pubmed] PHST- 2006/09/12 09:00 [medline] PHST- 2006/03/02 09:00 [entrez] AID - 91743 [pii] AID - 10.1159/000091743 [doi] PST - ppublish SO - Biol Neonate. 2006;90(1):34-9. doi: 10.1159/000091743. Epub 2006 Feb 23.