title: A novel assay to detect nucleotide receptor P2X7 genetic polymorphisms influencing numerous innate immune functions.
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.
authors.affiliation: Departments of Medicine and Biomolecular Chemistry, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA. ldenling@wisc.edu
authors.forename: Loren C
authors.initials: LC
authors.lastname: Denlinger
authors.forename: Kathleen
authors.initials: K
authors.lastname: Schell
authors.forename: Giuditta
authors.initials: G
authors.lastname: Angelini
authors.forename: Dawn
authors.initials: D
authors.lastname: Green
authors.forename: Arturo
authors.initials: A
authors.lastname: Guadarrama
authors.forename: Usha
authors.initials: U
authors.lastname: Prabhu
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Coursin
authors.forename: Kirk
authors.initials: K
authors.lastname: Hogan
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bertics
mesh_terms: 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
chemical_list: C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7