Abstract
We investigated cord and adult production of granulocyte-macrophage colony-stimulating factor (GM-CSF), expression of GM-CSF mRNA from unstimulated and activated mononuclear cells, and the affinity and presence of GM-CSF receptors on mature effector cells in an attempt to better understand the underlying pathophysiology of altered neonatal host defense. Utilizing 125I-GM-CSF as a ligand, Scatchard analysis revealed the presence of a single class affinity GM-CSF receptor with similar binding characteristics on both cord and adult peripheral PMN (kd = 44 and 39 pM) for adult and cord, respectively. Additionally, there was no significant difference in the number of GM-CSF receptors on cord versus adult neutrophils. Using a sandwich ELISA for measuring GM-CSF levels, we found nondetectable levels from supernatants of unstimulated cord and adult mononuclear cells and serum from cord and adult peripheral blood. However, there was a significant difference between cord and adult GM-CSF production from stimulated phytohemagglutinin and phorbol-12-myristate-6-acetate mononuclear cells (p < 0.02). Additionally, GM-CSF mRNA expression from activated cord mononuclear cells was significantly reduced after 6 h of stimulation compared with adults. Nuclear run-on experiments revealed no difference in transcriptional activation from activated cord and adult mononuclear cells. Actinomycin D transcriptional decay studies, however, demonstrated reduced GM-CSF half-life from activated cord versus adult mononuclear cells (t1/2 30 versus 100 min). These results suggest normal affinity and numbers of GM-CSF receptors on peripheral mature effector cells but decreased GM-CSF production and GM-CSF mRNA expression from activated cord versus adult mononuclear cells. Reduced GM-CSF mRNA expression and production may explain in part the difference in host defense between the newborn and the adult during states of increased demand.
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Cairo, M., Suen, Y., Knoppel, E. et al. Decreased Stimulated GM-CSF Production and GM-CSF Gene Expression but Normal Numbers of GM-CSF Receptors in Human Term Newborns Compared with Adults. Pediatr Res 30, 362–367 (1991). https://doi.org/10.1203/00006450-199110000-00013
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DOI: https://doi.org/10.1203/00006450-199110000-00013
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