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.