Effects of heat shock and hypoxia on neonatal neutrophil lipopolysaccharide responses: altered apoptosis, Toll-like receptor-4 and CD11b expression compared with adults.
BACKGROUND
Dysfunctional inflammatory responses have been implicated in several neonatal inflammatory disorders following infection and hypoxia.


OBJECTIVE
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.
Molloy
Eleanor J
EJ
Department of Surgery, Conway Institute of Biomolecular and Biomedical Research, Mater Misericordiae University Hospital, Dublin, Ireland. elesean@hotmail.com
O'Neill
Amanda J
AJ
Doyle
Belinda T
BT
Grantham
Julie J
JJ
Taylor
Cormac T
CT
Sheridan-Pereira
Margaret
M
Fitzpatrick
John M
JM
Webb
David W
DW
Watson
R William G
RW
D000328:Adult; D000375:Aging / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects; D039481:CD11b Antigen / Q000235:genetics*; D015687:Cell Hypoxia; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005865:Gestational Age; D006358:Hot Temperature; D006801:Humans; D007231:Infant, Newborn; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D039481:CD11b Antigen; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4