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

Abstract

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 50μg/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±217pg/ml, mean±sem, WT versus KO) and fetal plasma (774±673 versus 427±121pg/ml, WT versus KO). Peak concentrations occurred 2h after injection in WT dams (572542±41262pg/ml) and 4h in KO dams (616100±96300pg/ml). Therefore, in mice, a functional G-CSFR is not essential for the transfer of rhG-CSF from pregnant dams to their fetuses.