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.
MeSH terms
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Adenosine Triphosphate / metabolism*
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Adenosine Triphosphate / pharmacology
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Animals
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Apoptosis Regulatory Proteins / metabolism
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Apoptosis*
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Benzoxazoles / metabolism
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Benzoxazoles / pharmacokinetics
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Blotting, Western
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Calcium-Binding Proteins / metabolism
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Carrier Proteins / metabolism
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Caspase 1 / metabolism
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Cell Movement
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Cell Survival
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Cells, Cultured
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Connexins / genetics
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Connexins / metabolism*
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DNA-Binding Proteins
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Flow Cytometry
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Inflammasomes / metabolism*
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Interleukin-18 / metabolism
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Interleukin-1beta / metabolism
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Macrophages / cytology
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Macrophages / metabolism
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Macrophages, Peritoneal / cytology
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Macrophages, Peritoneal / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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NLR Family, Pyrin Domain-Containing 3 Protein
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Nuclear Proteins / metabolism
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Quinolinium Compounds / metabolism
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Quinolinium Compounds / pharmacokinetics
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Receptors, Purinergic P2X7 / genetics
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Receptors, Purinergic P2X7 / metabolism
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Thymus Gland / cytology
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Thymus Gland / metabolism
Substances
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Aim2 protein, mouse
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Apoptosis Regulatory Proteins
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Benzoxazoles
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Calcium-Binding Proteins
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Carrier Proteins
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Connexins
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DNA-Binding Proteins
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Inflammasomes
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Interleukin-18
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Interleukin-1beta
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Ipaf protein, mouse
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NLR Family, Pyrin Domain-Containing 3 Protein
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Nerve Tissue Proteins
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Nlrp3 protein, mouse
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Nuclear Proteins
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Panx1 protein, mouse
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Quinolinium Compounds
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Receptors, Purinergic P2X7
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YO-PRO 1
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Adenosine Triphosphate
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Caspase 1