Related Experiment Video
Updated: Aug 24, 2026
A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
Published on: April 1, 2019
A novel assay to detect nucleotide receptor P2X7 genetic polymorphisms influencing numerous innate immune functions
Loren C Denlinger1, Kathleen Schell, Giuditta Angelini
1Departments of Medicine and Biomolecular Chemistry, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA. ldenling@wisc.edu
Abstract:
The importance of accessory signaling pathways amplifying endotoxin responses has recently been highlighted by genetic studies describing LPS-hyporesponsive individuals despite carrying the common allele for TLR4. The nucleotide receptor P2X7 modulates the production of numerous LPS-stimulated inflammatory mediators. We have recently described the largest phenotypic screen known for genetic polymorphisms associated with the nucleotide receptor P2X7, a global regulator of leukocyte function. This required the development of a novel monocyte pore assay with numerous advantages over previous methods and with the potential to facilitate rapid (< 3 h), multiplex analysis of clinical samples. This paper addresses aspects pertinent to the development of the monocyte pore assay, briefly summarizes our results suggesting that P2X7 alleles modulate LPS-stimulated cytokine production, and discusses a model wherein P2X7 may serve as an amplification loop of innate immunity.
Insights
Genetic variations in the P2X7 receptor influence inflammatory responses to lipopolysaccharide (LPS). Our study developed a novel monocyte pore assay to analyze these P2X7 alleles and their impact on cytokine production, revealing P2X7
Area of Science:
- Immunology
- Genetics
- Cell Biology
Background:
- Accessory signaling pathways amplify endotoxin (lipopolysaccharide, LPS) responses.
- Genetic studies reveal LPS-hyporesponsive individuals despite common TLR4 alleles.
- The nucleotide receptor P2X7 modulates LPS-stimulated inflammatory mediator production.
Purpose of the Study:
- To describe the largest phenotypic screen for genetic polymorphisms in the P2X7 receptor.
- To develop a novel monocyte pore assay for rapid, multiplex analysis of clinical samples.
- To investigate how P2X7 alleles modulate LPS-stimulated cytokine production.
Main Methods:
- Development of a novel monocyte pore assay.
- Phenotypic screening of genetic polymorphisms in P2X7.
- Analysis of LPS-stimulated cytokine production.
Main Results:
- P2X7 alleles were identified as modulators of LPS-stimulated cytokine production.
- The novel monocyte pore assay allows for rapid (<3h) multiplex analysis.
- Genetic variations in P2X7 impact innate immune responses.
Conclusions:
- P2X7 receptor genetic polymorphisms significantly influence innate immune responses to LPS.
- The developed monocyte pore assay is a valuable tool for clinical sample analysis.
- P2X7 may function as an amplification loop in innate immunity.
