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Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation.

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.

Pubmed ID: 21508259

Authors

  • Qu Y
  • Misaghi S
  • Newton K
  • Gilmour LL
  • Louie S
  • Cupp JE
  • Dubyak GR
  • Hackos D
  • Dixit VM

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Data

June 1, 2011

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM036387
  • Agency: NIGMS NIH HHS, Id: R01 GM036387-22
  • Agency: NIGMS NIH HHS, Id: R01 GM036387-23

Mesh Terms

  • Adenosine Triphosphate
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Benzoxazoles
  • Blotting, Western
  • Calcium-Binding Proteins
  • Carrier Proteins
  • Caspase 1
  • Cell Movement
  • Cell Survival
  • Cells, Cultured
  • Connexins
  • DNA-Binding Proteins
  • Flow Cytometry
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • Macrophages
  • Macrophages, Peritoneal
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Quinolinium Compounds
  • Receptors, Purinergic P2X7
  • Thymus Gland