Deficient interferon-gamma receptor-mediated signaling in neonatal macrophages.

AIM

To describe functional and molecular characteristics of interferon-gamma (IFN-gamma) activation in neonatal mononuclear phagocytes (monocytes and macrophages).

METHODS AND RESULTS

Exposure of cord and adult macrophages to IFN-gamma gave quantitatively different results in Candida killing, as well as in release of superoxide anion (O2-). At concentrations of 100 U ml(-1) IFN-gamma, maximal increase in these functions with adult macrophages was achieved, whereas no enhancement of killing and O2- release by cord macrophages could be detected. Expression of IFN-gamma receptors was comparable on cord and adult cells and specific binding of [125I]IFN-gamma to cord monocytes and macrophages was even higher compared with adult cells. By flow cytometry, elements of IFN-gamma receptor-mediated signaling in cord and adult monocytes and macrophages were studied. Monoclonal antibodies against the native form of the signal transducer and activator of transcription-1 (STAT-1) revealed comparable expression of this protein in cord and adult macrophages. However, STAT-1 phosphorylation in response to IFN-gamma was significantly decreased in neonatal monocytes (p < 0.05) and macrophages (p < 0.01) compared with adult cells.

CONCLUSION

These data suggest deficient cytokine receptor signaling in neonatal mononuclear phagocytes exposed to IFN-gamma.