Transfer of recombinant human granulocyte colony stimulating factor (rhG-CSF) from the maternal to the fetal circulation is not dependent upon a functional G-CSF-receptor.

Administration of granulocyte colony stimulating factor (G-CSF), a haematopoietic growth factor, to pregnant rats increases neutrophil production in the pups. The mechanism for the placental transfer is unknown, but it has been speculated to involve the placental G-CSF receptor (G-CSFR). The purpose of this study was to test that hypothesis. Pregnant mice were treated with a single subcutaneous dose of 50 microg/kg recombinant human G-CSF (rhG-CSF). Mice with an intact G-CSFR ("wild type", WT) and those with a homozygous deletion in the G-CSFR gene (G-CSFR deficient, "knock-out", KO) were studied. At intervals after injection, fetuses were delivered and maternal blood, amniotic fluid (AF) and fetal blood collected. G-CSF concentrations were measured using an enzyme linked immunosorbent assay specific for human G-CSF. Thirty minutes after injection, G-CSF was measurable in the AF (167+/-50 versus 445+/-217 pg/ml, mean+/-sem, WT versus KO) and fetal plasma (774+/-673 versus 427+/-121 pg/ml, WT versus KO). Peak concentrations occurred 2 h after injection in WT dams (572 542+/-41 262 pg/ml) and 4 h in KO dams (616 100+/-96 300 pg/ml). Therefore, in mice, a functional G-CSFR is not essential for the transfer of rhG-CSF from pregnant dams to their fetuses.

Granulocyte colony-stimulating factor in preterm and term pregnancy, parturition, and intra-amniotic infection.

OBJECTIVE: [corrected] To determine the sources of granulocyte colony-stimulating factor (G-CSF) in amniotic fluid and to examine its relation to labor and clinically diagnosed intra-amniotic infection. METHODS: We assessed G-CSF and G-CSF receptor expression in placentas (n = 50) from 5-40 weeks' gestation, and G-CSF concentrations were measured in amniotic fluid (n = 146), bronchoalveolar lavage fluid (n = 8), and paired maternal serum, cord blood, neonatal serum, and neonatal urine samples (n = 16). RESULTS: Immunohistochemical staining and messenger RNA analysis showed placental expression of G-CSF and G-CSF receptor throughout gestation. The number of decidual stromal cells expressing G-CSF receptor was significantly higher in women with intra-amniotic infection compared with women without infection (27 +/- 2 versus 18 +/- 3 cells per high power field, P =.02). Amniotic fluid concentrations of G-CSF were not significantly different in noninfected preterm compared with term samples (1708 +/- 1673 versus 1612 +/- 2100 pg/mL, P =.9). Labor was not associated with a significant increase in amniotic fluid G-CSF concentrations (1864 +/- 3151 versus 1612 +/- 2100 pg/mL, P =.77, term labor versus no labor; 3335 +/- 5364 versus 1708 +/- 1673 pg/mL, P =.09, preterm). Concentrations of G-CSF in maternal serum, amniotic fluid, bronchoalveolar lavage fluid, and neonatal urine were increased during intra-amniotic infection (all P <.05). CONCLUSION: Amniotic fluid G-CSF concentrations were similar in preterm and term pregnancies and were not significantly influenced by labor. Intra-amniotic infection was associated with an increased number of placental cells expressing the G-CSF receptor and higher concentrations of G-CSF in amniotic fluid, maternal serum, neonatal urine, and neonatal bronchoalveolar lavage samples.