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Human recombinant interferon gamma enhances neonatal polymorphonuclear leukocyte activation and movement, and
H R Hill1, N H Augustine, H S Jaffe
1Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132.
Abstract:
In previous studies, we have reported that after chemotactic factor stimulation, PMNs from neonates fail to undergo certain critical activation steps. Furthermore, the concentration of free intracellular calcium reached is significantly below that of PMNs from adults. Interferon-gamma (IFN-gamma) is a lymphokine that has been shown to activate phagocytic cells, and IFN-gamma messenger RNA production by neonatal mononuclear leukocytes has been reported to be depressed. In the present studies, we found that recombinant human IFN-gamma markedly enhanced the chemotactic responses of PMNs from neonates to levels that were not different from that of PMNs from adults. Furthermore, preincubation of the neonatal cells with this recombinant human lymphokine also corrected the abnormality in intracellular calcium metabolism. These results suggest that this developmental defect in phagocytic cell movement may be the result of an intrinsic defect in IFN-gamma production resulting in deficiency of this critical phagocyte-activating lymphokine.
Insights
Neonatal neutrophils exhibit impaired chemotaxis and calcium signaling. Supplementation with Interferon-gamma (IFN-gamma) corrected these defects, suggesting a deficiency in this immune-boosting lymphokine contributes to impaired neonatal immune responses.
Area of Science:
- Immunology
- Neonatal immunology
- Cellular immunology
Background:
- Neonatal neutrophils (PMNs) show impaired activation and reduced intracellular calcium levels upon stimulation.
- Production of Interferon-gamma (IFN-gamma) by neonatal leukocytes is reportedly depressed.
- Deficiencies in PMN function can compromise neonatal immune defense.
Purpose of the Study:
- To investigate the effect of Interferon-gamma (IFN-gamma) on neonatal neutrophil function.
- To determine if IFN-gamma can correct impaired chemotaxis and calcium metabolism in neonatal PMNs.
- To explore the role of IFN-gamma deficiency in neonatal immune cell defects.
Main Methods:
- Treatment of neonatal PMNs with recombinant human IFN-gamma.
- Assessment of neutrophil chemotactic response.
- Measurement of intracellular calcium levels in neonatal PMNs.
Main Results:
- Recombinant human IFN-gamma significantly enhanced neonatal PMN chemotaxis to adult levels.
- IFN-gamma pre-treatment corrected the abnormal intracellular calcium metabolism in neonatal PMNs.
- Neonatal PMN dysfunction may stem from insufficient endogenous IFN-gamma.
Conclusions:
- IFN-gamma administration can restore normal chemotactic and calcium signaling functions in neonatal neutrophils.
- A deficiency in IFN-gamma may underlie the impaired phagocytic cell movement observed in neonates.
- Restoring IFN-gamma levels could be a therapeutic strategy to enhance neonatal immune responses.