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 productio n and enhances neutrophil function. The effects of G-CSF are mediated by bi nding to its receptor. Since neutrophils are an essential part of the neona tal host defense system, we studied G-CSF receptor expression in neonatal n eutrophils. 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 re combinant 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 compare d to adults (61 +/- 6 vs, 89 +/- 2%). G-CSF receptor mRNA transcripts of ne utrophils from newborns compared to adults was lower, too (77 +/- 14 vs. 15 2 +/- 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 e xpression. TNF-alpha, however, down-regulated G-CSF receptor expression, We conclude that low protein and mRNA expression of G-CSF receptor in neutrop hils 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 itsel f, but also by TNF-alpha, Copyright (C) 2000 S. Kargar AG, Basel.