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Updated: Jul 10, 2026
An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
In vitro--transcriptional response of polymorphonuclear leukocytes following contact with different antigens
K Hochegger1, P Perco, J Enrich
1Division of Nephrology, Medical University Innsbruck, Anichstrasse 35, Innsbruck, Austria.
Abstract:
Background Human polymorphonuclear neutrophils (PMN) are activated and undergo apoptosis if brought into contact with cuprophane haemodialysis membranes, a phenomenon not observed if more 'biocompatible' polysulfone dialysers are used. It remains yet to be defined if this differential response is due to mechanisms regulated on a transcriptional or protein level. Furthermore, it is not clear if the contact of PMN with membranes ('frustrated' phagocytosis) activates the same response as phagocytosis of bacteria (complete phagocytosis). Materials and methods We performed a genome-wide differential gene expression study using cDNA microarrays to analyse the impact of different dialysis fibres on the transcriptional response of PMN of human healthy volunteers. These results were compared to transcriptional response of PMN during phagocytosis of Escherichia coli. Results We did not detect significant differences in gene expression between PMN stimulated with cuprophane or pulysulfone. Compared to unstimulated PMN the 'frustrated' phagocytosis of either dialysis membrane resulted in increased expression of 50 genes, with a marked up-regulation of FOS - and JUN - transcripts, but with only little activation of immune response genes, and virtually no activation of apoptosis related RNA transcripts. In contrast, phagocytosis of E.coli was associated with a striking up-regulation of 88 genes, most of them involved in pro- and antiapoptotic pathways, immune response and activation of nuclear factor kappa B and inhibitor of NF-kappa B. Conclusions Our results suggest that the response of PMN to artificial surfaces is not controlled on transcriptional level. Complete and 'frustrated' phagocytosis activate markedly distinct transcriptional regulatory pathways in PMN.
Insights
Polymorphonuclear neutrophils (PMN) show distinct transcriptional responses to dialysis membranes versus bacterial phagocytosis. Dialysis membrane contact does not significantly alter PMN gene expression, unlike complete phagocytosis.
Area of Science:
- Immunology
- Cell Biology
- Biomaterials Science
Background:
- Human polymorphonuclear neutrophils (PMN) exhibit differential responses to cuprophane versus polysulfone hemodialysis membranes.
- The underlying mechanisms, whether transcriptional or protein-level, remain undefined.
- The distinction between 'frustrated' phagocytosis (membrane contact) and complete phagocytosis (bacterial ingestion) in PMN activation is unclear.
Purpose of the Study:
- To investigate the transcriptional response of PMN to different hemodialysis membranes.
- To compare the transcriptional profiles of PMN during 'frustrated' phagocytosis with those during complete phagocytosis of bacteria.
- To determine if PMN responses to artificial surfaces are regulated at the transcriptional level.
Main Methods:
- Genome-wide differential gene expression analysis using cDNA microarrays.
- Stimulation of human PMN with cuprophane and polysulfone dialysis membranes.
- Comparison of transcriptional responses to 'frustrated' phagocytosis and complete phagocytosis of Escherichia coli.
Main Results:
- No significant gene expression differences were observed between PMN stimulated with cuprophane or polysulfone membranes.
- Frustrated phagocytosis of dialysis membranes led to the up-regulation of 50 genes, including FOS and JUN, with minimal immune or apoptosis gene activation.
- Complete phagocytosis of E. coli induced a striking up-regulation of 88 genes involved in apoptosis, immune response, and NF-kappa B signaling.
Conclusions:
- The transcriptional response of PMN to artificial surfaces is not significantly altered.
- Complete phagocytosis and 'frustrated' phagocytosis activate markedly distinct transcriptional regulatory pathways in PMN.
- Hemodialysis membrane interactions do not trigger the same transcriptional cascade as bacterial phagocytosis.
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