Neutrophil Pool Sizes and Granulocyte Colony-Stimulating Factor Production in Human Mid-Trimester Fetuses

ABSTRACT: We quantified neutrophils and neutrophil progenitors, and assessed granulocyte colony-stimulating factor (G-CSF) production in the liver and bone marrow of 20 human abortuses after elective pregnancy termination between 14 and 24 wk of gestation. Mature neutrophils were not observed in any of the liver specimens, but were present in the bone marrow as early as 14 wk. The concentrations of neutrophils in the fetal marrow were extremely low, by comparison with term infants and adults, with less than 5% of the nucleated cells being segmented neutrophils, band neutrophils, or metamyelocytes compared with 31–69% in term infants. Despite the low neutrophil populations, progenitors which had the capacity for clonal maturation into neutrophils in vitro were abundant in the fetal liver and fetal bone marrow. In addition, such progenitors had a dose-response relationship to recombinant G-CSF similar to that of progenitors from the bone marrow of healthy adults. At each gestational age tested, stimulation of mononuclear cells from fetal liver with IL-1α generated less G-CSF protein and fewer G-CSF mRNA transcripts than did stimulation of mononuclear cells from fetal bone marrow. Mononuclear cells from the fetal bone marrow produced less G-CSF protein and mRNA than did mononuclear cells from the blood of adults. Thus, the liver of the mid-trimester human fetus is almost devoid of neutrophils, and the bone marrow contains a significantly lower proportion of neutrophils than does the marrow of term neonates or adults. These findings correlate with IL-1α-induced production of G-CSF in these organs. The lack of G-CSF production might explain the small neutrophil reserves found in extremely preterm infants.