A novel assay to detect nucleotide receptor P2X7 genetic polymorphisms influencing numerous innate immune functions.
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.
Denlinger
Loren C
LC
Departments of Medicine and Biomolecular Chemistry, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA. ldenling@wisc.edu
Schell
Kathleen
K
Angelini
Giuditta
G
Green
Dawn
D
Guadarrama
Arturo
A
Prabhu
Usha
U
Coursin
Douglas B
DB
Hogan
Kirk
K
Bertics
Paul J
PJ
D019943:Amino Acid Substitution; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007962:Leukocytes / Q000276:immunology; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058486:Receptors, Purinergic P2X7
C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7