Abstract
ABSTRACT: Impaired production and delivery of neutrophils to the site of infection have been implicated in the increased susceptibility of the neonate to infection. Because granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) play critical roles in the production of neutrophils from marrow precursors, we assessed the ability of leukocytes from neonates and adults to produce GM-CSF, G-CSF, and, for comparison, macrophage colony-stimulating factor (M-CSF) after stimulation with concanavalin A ± phorbol myristate acetate [blood mononuclear cells (MC) and T lymphocytes] or lipopolysaccharide (monocytes). MC and monocytes from adult and neonatal subjects produced mRNA for GM-CSF, G-CSF, and M-CSF, whereas T cells produced only GM-CSF mRNA. Neonatal MC and T cells accumulated only −30% as much GM-CSF mRNA as did adult MC and T cells. In contrast, the accumulation of GM-CSF mRNA by neonatal and adult monocytes was similar. Neonatal MC also accumulated similar amounts of G-CSF mRNA and somewhat more M-CSF mRNA than did adult MC; results with monocytes were similar to those with MC. Results of colony-stimulating activity bioassays on supernatants from neonatal and adult MC stimulated with concanavalin A paralleled the mRNA results. Although the overall number of colonies generated using neonatal and adult supernatants was similar, neonatal MC supernatants generated significantly more (p < 0.05) monocyte-containing colonies (72 ±19 versus 46 ± 11), significantly fewer (p < 0.05) eosinophil-containing colonies (7 ± 6 versus 23 ± 13), and similar numbers of granulocyte-containing colonies (59 ± 23 versus 63 ± 11) compared with adult MC supernatants. Because GM-CSF is a major determinant of eosinophil production in these assays, these data suggested diminished amounts of GM- CSF in the neonatal culture supernatants. Similarly, GM- CSF concentrations in neonatal MC and T cell culture supernatants averaged 40 to 50% of the concentrations in adult culture supernatants as determined by ELISA (p < 0.01). Whether the modestly diminished GM-CSF production by neonatal T cells contributes t the observed deficiency of granulocyte production in neonates, which occurs when demand is increased in response to infection, remains to be determined.
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English, B., Hammond, W., Lewis, D. et al. Decreased Granulocyte-Macrophage Colony-Stimulating Factor Production by Human Neonatal Blood Mononuclear Cells and T Cells. Pediatr Res 31, 211–216 (1992). https://doi.org/10.1203/00006450-199203000-00004
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DOI: https://doi.org/10.1203/00006450-199203000-00004
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