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 RIS Download
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 | NLR Family, Pyrin Domain-Containing 3 Protein | Nerve Tissue Proteins | Nuclear Proteins | Quinolinium Compounds | Receptors, Purinergic P2X7 | Thymus Gland