Neonatal Mononuclear Cell Metabolism: Further Evidence For Diminished Monocyte Function in the Neonate

Abstract

Summary: The metabolic capacity of neonatal monocytes was compared to the metabolic capacity of adult monocytes by two entirely different methods: the selective diminution of monocyte contamination of whole mononuclear cells and the isolation of relatively purified populations of monocytes.

Monocyte removal from whole mononuclear cells produced a diminution in the pyruvate kinase (PK) activity (from 28.6 ± 1.1 to 15.6 ± 1.2 nmoles/min/10⁷ cells) and an increase in adenosine triphosphate (ATP) content (from 7.9 ± 1.0 to 9.5 ± 0.8 nmoles/10⁷ cells) in adult cells. No change in PK activity (from 13.5 ±1.3 to 14.0 ± 1.3) was observed in cord cells, but the ATP content of cord cells was higher after monocyte depletion (from 4.7 ± 0.5 to 6.2 ± 0.7).

The suggestion of metabolic vulnerability was confirmed by metabolic analysis of isolated adult and cord monocytes. The PK activity of adult monocytes was greater than that of cord monocytes (57 ± 9 and 25 ± 0.3, respectively) and the ATP content of adult monocytes (5.7 ± 0.2) was greater than that of cord monocytes (2.3 ± 0.1).

The data confirm prior observations of diminished energy metabolism in neonatal mononuclear cells and suggest that the metabolic perturbations may, in part, correlate with functional immaturity of the neonatal monocyte.

Speculation: Monocytes have a glycolytic rate that far exceeds that of other mononuclear cells. The presence of an increased rate of energy synthesis, however, is not accompanied by an increase in ATP content. The metabolic requirements of monocytes are, therefore, greater than for other mononuclear cells. This suggests that monocytes may be susceptible to dysfunction secondary to metabolic stress (increased metabolic requirements or diminished metabolic capacity). The neonatal monocyte appears to be much more metabolically vulnerable than the adult monocyte and this may, in part, account for the immune dysfunction observed in the newborn infant.

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