Decreased mRNA expression of G-CSF receptor in cord blood neutrophils of term newborns: regulation of expression by G-CSF and TNF-alpha.
Granulocyte colony-stimulating factor (G-CSF) promotes neutrophil production and enhances neutrophil function. The effects of G-CSF are mediated by binding to its receptor. Since neutrophils are an essential part of the neonatal host defense system, we studied G-CSF receptor expression in neonatal neutrophils. We determined protein and mRNA expression of G-CSF receptor in freshly isolated neutrophils from cord blood of healthy term newborns (n = 16) and of adults (n = 6) as well as the in vitro effect of supplemented recombinant human G-CSF (rhG-CSF) and tumor necrosis factor-alpha (TNF-alpha) on G-CSF receptor expression of neutrophils. Expression of G-CSF receptor on the surface of neutrophils of cord blood was significantly lower compared to adults (61 +/- 6 vs. 89 +/- 2%). G-CSF receptor mRNA transcripts of neutrophils from newborns compared to adults was lower, too (77 +/- 14 vs. 152 +/- 33%). Neutrophils isolated from cord blood showed a decrease of G-CSF receptor expression within 24 h of culture. Moreover, we were able to show that supplemented rhG-CSF is necessary for maintenance of G-CSF receptor expression. TNF-alpha, however, down-regulated G-CSF receptor expression. We conclude that low protein and mRNA expression of G-CSF receptor in neutrophils of neonates compared to adults may adversely affect granulopoiesis and neutrophil functions by decreased responsiveness to G-CSF. Furthermore, G-CSF receptor expression on neutrophils was modified not only by G-CSF itself, but also by TNF-alpha.
Gessler
P
P
University Children's Hospital, Department of Neonatology, Tübingen, Germany. peter.gessler@insel.ch
Neu
S
S
Brockmann
Y
Y
Speer
C P
CP
D000328:Adult; D005312:Fetal Blood / Q000166:cytology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000097:blood*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor