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Induction of interferon-gamma by cord blood mononuclear cells is calcium dependent

A M Kesson1, Y J Bryson

  • 1Department of Pediatrics, UCLA School of Medicine 90024.

Cellular Immunology
|March 1, 1991
PubMed

Insights

Human cord blood cells have lower interferon-gamma (IFN-gamma) production. Adding calcium chloride or macrophage mediators enhances IFN-gamma, indicating a calcium-dependent pathway is key.

Area of Science:

  • Immunology
  • Cellular Biology
  • Molecular Medicine

Background:

  • Human cord blood mononuclear cells (MNCs) exhibit diminished interferon-gamma (IFN-gamma) production compared to adult MNCs.
  • This deficiency is partly attributed to the absence of a soluble mediator derived from macrophages.

Purpose of the Study:

  • To investigate the mechanisms underlying the impaired IFN-gamma production in neonatal MNCs.
  • To identify soluble factors and intracellular signaling pathways involved in regulating IFN-gamma synthesis.

Main Methods:

  • Stimulation of cord blood MNCs with phytohemagglutinin (PHA) and analysis of IFN-gamma production.
  • Addition of adult macrophage supernatants or U937 cell supernatants to neonatal MNC cultures.
  • Assessment of the role of calcium ions (CaCl2) and calcium channel blockers (MnCl2, chlorpromazine, verapamil) in modulating IFN-gamma production.

Main Results:

  • Supernatants from stimulated adult macrophages and U937 cells significantly increased IFN-gamma production in neonatal MNCs.
  • Exogenous calcium chloride (CaCl2) supplementation mimicked the effect of the soluble mediators, enhancing IFN-gamma production.
  • The enhancing effects of both soluble mediators and CaCl2 were blocked by calcium channel inhibitors, suggesting a calcium-dependent signaling mechanism.

Conclusions:

  • Soluble factors from adult macrophages and U937 cells enhance IFN-gamma production in cord blood MNCs via calcium-dependent signaling.
  • Calcium influx appears to be a critical component in overcoming the IFN-gamma production defect in neonatal immune cells.

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