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Phagocytosis of opsonized yeast induces tumor necrosis factor-alpha mRNA accumulation and protein release by human
F Bazzoni1, M A Cassatella, C Laudanna
1Institute of General Pathology, University of Verona, Italy.
Abstract:
In this report we show that phagocytosis of yeast particles opsonized with IgG (Y-IgG) by human polymorphonuclear cells (PMN) results in the selective induction of tumor necrosis factor (TNF-alpha) messenger RNA (mRNA) and release of its mature protein. Lipopolysaccharide (LPS) was also found able to induce TNF-alpha secretion by PMN, but was a less potent stimulus compared with Y-IgG. There was no evidence of interleukin-6 (IL-6) gene expression in PMN after phagocytosis of Y-IgG or in response to LPS, whereas IL-6 mRNA expression and secretion were induced by either stimulus in monocytes. These findings demonstrate that a physiological function such as phagocytosis modulates the gene expression for a cytokine in PMN and shed new light on the understanding of the pathogenesis of the inflammatory process.
Insights
Phagocytosis of yeast particles by human immune cells selectively induces tumor necrosis factor-alpha (TNF-alpha) mRNA and protein. This process, unlike with lipopolysaccharide (LPS), does not activate interleukin-6 (IL-6) in polymorphonuclear cells.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Phagocytosis is a critical cellular process for immune defense.
- Cytokine gene expression in immune cells is complex and stimulus-dependent.
- Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are key inflammatory mediators.
Purpose of the Study:
- To investigate the effect of phagocytosis on cytokine gene expression in human polymorphonuclear cells (PMN).
- To compare the potency of yeast-opsonized IgG (Y-IgG) and lipopolysaccharide (LPS) in inducing cytokine production in PMN.
- To examine the differential expression of TNF-alpha and IL-6 in PMN and monocytes.
Main Methods:
- Human polymorphonuclear cells (PMN) and monocytes were isolated.
- Cells were stimulated with yeast particles opsonized with IgG (Y-IgG) or lipopolysaccharide (LPS).
- Messenger RNA (mRNA) expression for TNF-alpha and IL-6 was analyzed using molecular techniques.
- Protein secretion of TNF-alpha and IL-6 was measured.
Main Results:
- Phagocytosis of Y-IgG by PMN selectively induced TNF-alpha mRNA and protein release.
- LPS also induced TNF-alpha secretion in PMN, but was a less potent stimulus than Y-IgG.
- Neither Y-IgG nor LPS induced IL-6 gene expression or secretion in PMN.
- Both stimuli induced IL-6 mRNA expression and secretion in monocytes.
Conclusions:
- Phagocytosis is a potent stimulus for TNF-alpha gene expression and production in human PMN.
- PMN exhibit distinct cytokine responses to Y-IgG and LPS, with selective TNF-alpha induction.
- Human monocytes display a different cytokine profile, responding to both stimuli with IL-6 production.
- These findings highlight how physiological functions modulate cytokine gene expression, advancing the understanding of inflammatory processes.