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.
Calhoun
D A
DA
Division of Neonatology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32620-0296, USA. calhoda@peds.ufl.edu
Gersting
J A
JA
Lunøe
M
M
Du
Y
Y
Christensen
R D
RD
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D017353:Gene Deletion; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor