title: Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation.
abstract: Apoptotic cell death is important for embryonic development, immune cell homeostasis, and pathogen elimination. Innate immune cells also undergo a very rapid form of cell death termed pyroptosis after activating the protease caspase-1. The hemichannel pannexin-1 has been implicated in both processes. In this study, we describe the characterization of pannexin-1-deficient mice. LPS-primed bone marrow-derived macrophages lacking pannexin-1 activated caspase-1 and secreted its substrates IL-1β and IL-18 normally after stimulation with ATP, nigericin, alum, silica, flagellin, or cytoplasmic DNA, indicating that pannexin-1 is dispensable for assembly of caspase-1-activating inflammasome complexes. Instead, thymocytes lacking pannexin-1, but not the P2X7R purinergic receptor, were defective in their uptake of the nucleic acid dye YO-PRO-1 during early apoptosis. Cell death was not delayed but, unlike their wild-type counterparts, Panx1(-/-) thymocytes failed to recruit wild-type peritoneal macrophages in a Transwell migration assay. These data are consistent with pannexin-1 liberating ATP and other yet to be defined "find me" signals necessary for macrophage recruitment to apoptotic cells.
authors.affiliation: Physiological Chemistry Department, Genentech, Inc, South San Francisco, CA 94080, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qu
authors.forename: Shahram
authors.initials: S
authors.lastname: Misaghi
authors.forename: Kim
authors.initials: K
authors.lastname: Newton
authors.forename: Laurie L
authors.initials: LL
authors.lastname: Gilmour
authors.forename: Salina
authors.initials: S
authors.lastname: Louie
authors.forename: James E
authors.initials: JE
authors.lastname: Cupp
authors.forename: George R
authors.initials: GR
authors.lastname: Dubyak
authors.forename: David
authors.initials: D
authors.lastname: Hackos
authors.forename: Vishva M
authors.initials: VM
authors.lastname: Dixit
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001583:Benzoxazoles / Q000378:metabolism / Q000493:pharmacokinetics; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011806:Quinolinium Compounds / Q000378:metabolism / Q000493:pharmacokinetics; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism
chemical_list: C540422:Aim2 protein, mouse; D051017:Apoptosis Regulatory Proteins; D001583:Benzoxazoles; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D017630:Connexins; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; C512299:Ipaf protein, mouse; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009419:Nerve Tissue Proteins; C492716:Nlrp3 protein, mouse; D009687:Nuclear Proteins; C503631:Panx1 protein, mouse; D011806:Quinolinium Compounds; D058486:Receptors, Purinergic P2X7; C089813:YO-PRO 1; D000255:Adenosine Triphosphate; D020170:Caspase 1