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Transforming growth factor-beta 1, macrophage inflammatory protein-1 alpha,
and interleukin-8 gene expression is lower in stimulated human neonatal
compared with adult mononuclear cells
M Chang, Y Suen, SM Lee, D Baly, JS Buzby, E Knoppel, S Wolpe and MS Cairo
Children's Hospital of Orange County, CA 92668.
Hematopoiesis is developmentally immature in the newborn compared with the
adult. Diminished gene expression of several positive hematopoietic
regulators has been observed in activated cord compared with adult
peripheral blood mononuclear cells (MNC; Cairo et al. Pediatr Res, 30:362,
1991 and Cairo et al, Pediatr Res, 31:574, 1992). However, altered
expression of negative hematopoietic regulators during states of increased
demand may also contribute to the pathogenesis of newborn dyshematopoiesis.
To test this hypothesis, we measured protein levels of transforming growth
factor-beta 1 (TGF-beta 1) and macrophage inflammatory protein-1 alpha
(MIP-1 alpha) in the conditioned media of human umbilical cord and adult
MNC using specific enzyme-linked immunosorbent assays. There was
significantly less TGF-beta 1 in culture supernatants of cord versus adult
MNC after 24, 72, and 120 hours of stimulation (P < .05), and
significantly less MIP-1 alpha in cord versus adult supernatants after 72
hours and 120 hours of stimulation (P < .01). We then examined the mRNA
expression of the negative regulators TGF-beta 1, MIP-1 alpha, and
interleukin-8 (IL-8) in cord and adult MNC using Northern blot
hybridization followed by quantitative densitometry. Cord MNC expressed
significantly less TGF- beta 1 mRNA than adult MNC 6 hours and 72 hours
after stimulation (P < .001). Cord MNC expressed significantly less
MIP-1 alpha mRNA than adult MNC 6 hours (P < .01), 24 hours (P <
.001), and 72 hours after stimulation (P < .001). Cord MNC also
expressed significantly less IL-8 mRNA than adult MNC 6 hours after
stimulation (P < .001). Therefore, decreased mRNA accumulation appears
to coincide with reduced cytokine expression in the activated cord MNC.
There were no significant differences in the transcription rates determined
by nuclear run-on assay of either the TGF-beta 1 or MIP-1 alpha gene in
cord versus adult MNC after 6 hours of stimulation, suggesting that the
reduced TGF-beta 1 and MIP-1 alpha mRNA in activated cord MNC may be
secondary to alteration in posttranscriptional regulation. The present
results, together with those of our previous studies, suggest that the
altered expression of both positive and negative hematopoietic regulators
may be involved in the immaturity of host defense in human neonates.
Volume 84,
Issue 1,
pp. 118-124,
07/01/1994
Copyright © 1994 by The American Society of Hematology
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