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-la 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 The NSP is the sum of all segmented neutrophils, band neutrophils, and metamyelocytes held in reserve for ready release into the circulation (1). Rat pups delivered prematurely have a much smaller NSP, per g of body weight, than do those delivered at term, and pups delivered at term have a smaller NSP than do adult rats (2-6). It is unknown, however, whether this observation applies to humans. Studies employing cells

Spontaneous and Fas-mediated apoptosis are diminished in umbilical cord blood neutrophils compared with adult neutrophils

“…Because the bone marrow PMN storage pool is small in the developing fetus and neonate [57][58][59], a prolonged survival of circulating PMN may be necessary to accumulate an adequate marrow PMN reserve, and thus a delay in apoptosis of Cord blood (CB) and adult (AD) PMN were cultured in the presence of increasing concentrations of rhGM-CSF (shown above as ng/mL). Data shown are percent inhibition of PMN apoptosis by rhGM-CSF compared with apoptosis of PMN cultured in media alone; n, number of paired experiments, mean Ϯ SD.…”

Differential Maturation of the Innate Immune Response in Human Fetuses

“…Evidence of this is provided by the pattern of infections closely resembling that seen in profound neutropenia (4). Depleted neutrophil storage pools and neutropenia were described to be associated with neonatal sepsis and are negative predictors of outcome (5,6). Several qualitative deficiencies of phagocyte function were demonstrated earlier in preterm infants and stressed or septic neonates.…”

Messenger RNA Expression of Granulocyte Colony-Stimulating Factor Receptor Isoforms in the Fetus

“…Previously, we reported the expression of G-CSF-R in fetal hematopoietic tissues [18,19] and in fetal non-hematopoietic tissues [9]. In the present study, we used RT-PCR to see that the seven known isoforms of the G-CSF-R have different patterns of mRNA expression in various hematopoietic and Representative gels for a PCR with primers used with each of the primary tissues at 18 weeks gestation.…”