Induction of interferon-gamma by cord blood mononuclear cells is calcium dependent.
Human cord blood mononuclear cells (MNCs) are deficient in their ability to produce interferon-gamma (IFN-gamma). Previous studies have shown that phytohemagglutinin (PHA)-stimulated neonatal MNCs produced significantly less IFN-gamma than adult PHA-stimulated MNCs. The deficient IFN-gamma production is partly due to the absence of a macrophage-derived soluble mediator. Supernatants from PHA-stimulated adult macrophages and phorbol myristate acetate (PMA)-stimulated U937 cells (which were dialyzed prior to culture to remove PMA) increased IFN-gamma production in neonatal PHA-stimulated MNC (14 to 217 units/ml and 14 to 293 units/ml, respectively). The requirement for a soluble macrophage mediator was replaced by the addition of exogenous calcium chloride (CaCl2) to PHA-stimulated cord blood MNCs. The increase in IFN-gamma production by exogenous CaCl2 was blocked by the addition of the calcium channel blocker, manganese chloride (MnCl2). Furthermore, the increased IFN-gamma production by PHA-stimulated cord blood MNC in the presence of PHA-stimulated adult macrophage supernatant or PMA-stimulated U937 supernatant was abrogated by the addition of MnCl2, chlorpromazine, and verapamil. These data suggested that the soluble factor produced by PHA-stimulated adult macrophage supernatant and PHA-stimulated U937 supernatant induced IFN-gamma production in PHA-stimulated cord blood MNC by inducing calcium-dependent signals at more than one site.
Kesson
A M
AM
Department of Pediatrics, UCLA School of Medicine 90024.
Bryson
Y J
YJ
D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology; D002460:Cell Line; D002712:Chlorides; D002746:Chlorpromazine / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008264:Macrophages / Q000502:physiology; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D010835:Phytohemagglutinins / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002147:Calmodulin; D002712:Chlorides; D017895:Manganese Compounds; D010835:Phytohemagglutinins; D008345:Manganese; D007371:Interferon-gamma; D014700:Verapamil; C025340:manganese chloride; D002118:Calcium; D002746:Chlorpromazine