NEUTROPHIL POOL SIZES AND GRANULOCYTE-COLONY-STIMULATING FACTOR PRODUCTION IN HUMAN MIDTRIMESTER FETUSES

We quantified neutrophils and neutrophil progenitors, and assessed gra nulocyte colony-stimulating factor (G-CSF) production in the liver and bone marrow of 20 human abortuses after elective pregnancy terminatio n between 14 and 24 wk of gestation. Mature neutrophils were not obser ved 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 mar row were extremely low, by comparison with term infants and adults, wi th less than 5% of the nucleated cells being segmented neutrophils, ba nd neutrophils, or metamyelocytes compared with 31-69% in term infants . Despite the low neutrophil populations, progenitors which had the ca pacity for clonal maturation into neutrophils in vitro were abundant i n 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 gestat ional age tested, stimulation of mononuclear cells from fetal liver wi th IL-1 alpha generated less G-CSF protein and fewer G-CSF mRNA transc ripts than did stimulation of mononuclear cells from fetal bone marrow . Mononuclear cells from the fetal bone marrow produced less G-CSF pro tein and mRNA than did mononuclear cells from the blood of adults. Thu s, the liver of the mid-trimester human fetus is almost devoid of neut rophils, 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-1 alpha-induced production of G-CSF in the se organs. The lack of G-CSF production might explain the small neutro phil reserves found in extremely preterm infants.