Decreased stimulated GM-CSF production and GM-CSF gene expression but normal numbers of GM-CSF receptors in human term newborns compared with adults.
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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Cairo
M S
MS
Division of Hematology/Oncology, Children's Hospital of Orange County, California 92668.
Suen
Y
Y
Knoppel
E
E
van de Ven
C
C
Nguyen
A
A
Sender
L
L
D000328:Adult; D000375:Aging / Q000378:metabolism*; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D005312:Fetal Blood; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D009504:Neutrophils / Q000378:metabolism; D012313:RNA / Q000302:isolation & purification
D003115:Colony-Stimulating Factors; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor