Cytokine receptor signalling in neonatal macrophages: defective STAT-1 phosphorylation in response to stimulation with IFN-gamma.
We reported earlier that neonatal monocyte-derived macrophages (MDM) could not be fully activated with IFN-gamma, a finding that could not be attributed to lower expression of IFN-gamma receptors on the neonatal cells. In this study we explored elements of IFN-gamma R-mediated signalling in cord monocytes and MDM. Intracellular expression of STAT-1 was analysed by flow cytometry. We have assessed phosphorylation of STAT-1 by using MoAbs that distinguish native and phosphorylated forms of STAT-1 on a discrete cell basis. Using MoAbs against the native form of STAT-1 revealed comparable expression of this protein in cord and adult cells (both monocytes and MDM). However, STAT-1 phosphorylation in response to IFN-gamma was significantly decreased in neonatal monocytes (P < 0.05) and MDM (P < 0.01) compared to adult cells (n > 5 for each). These data suggest deficient cytokine-receptor signalling in neonatal mononuclear phagocytes exposed to IFN-gamma. We propose that decreased STAT-1 phosphorylation and activation may represent developmental immaturity and may contribute to the unique susceptibility of neonates to infections by intracellular pathogens.
Maródi
L
L
Department of Infectology and Paediatric Immunology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. lmarodi@jaguar.dote.hu
Goda
K
K
Palicz
A
A
Szabó
G
G
D000328:Adult; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D010766:Phosphorylation; D018121:Receptors, Cytokine / Q000378:metabolism*; D017471:Receptors, Interferon / Q000378:metabolism; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism*; D000096743:Interferon gamma Receptor
D004268:DNA-Binding Proteins; D007371:Interferon-gamma; D018121:Receptors, Cytokine; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human