Pannexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation.
Alexander W. Lohman,Igor L. Leskov,Joshua T. Butcher,Scott R. Johnstone,Tara A. Stokes,Daniela Begandt,Leon J. DeLalio,Angela K. Best,Silvia Penuela,Norbert Leitinger,Kodi S. Ravichandran,Karen Y. Stokes,Brant E. Isakson +12 more
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TLDR
It is reported that the ATP-release channel Pannexin1 (Panx1) opens downstream of EC activation by TNF-α, placing Panx1 channels at the centre of cytokine crosstalk with purinergic signalling in the endothelium.Abstract:
Inflammatory cell recruitment to local sites of tissue injury and/or infection is controlled by a plethora of signalling processes influencing cell-to-cell interactions between the vascular endothelial cells (ECs) in post-capillary venules and circulating leukocytes. Recently, ATP-sensitive P2Y purinergic receptors have emerged as downstream regulators of EC activation in vascular inflammation. However, the mechanism(s) regulating cellular ATP release in this response remains elusive. Here we report that the ATP-release channel Pannexin1 (Panx1) opens downstream of EC activation by TNF-α. This process involves activation of type-1 TNF receptors, recruitment of Src family kinases (SFK) and SFK-dependent phosphorylation of Panx1. Using an inducible, EC-specific Panx1 knockout mouse line, we report a previously unidentified role for Panx1 channels in promoting leukocyte adhesion and emigration through the venous wall during acute systemic inflammation, placing Panx1 channels at the centre of cytokine crosstalk with purinergic signalling in the endothelium.read more
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Book ChapterDOI
Regulation of Skeletal Muscle Myoblast Differentiation and Proliferation by Pannexins
TL;DR: The expression of pannexins and their post-translational modifications in skeletal muscle, their known functions in various steps of myogenesis, including myoblast proliferation and differentiation, as well as their possible roles in skeletal Muscle development, regeneration, and diseases such as Duchenne muscular dystrophy are discussed.
Journal ArticleDOI
Blocking connexin43 hemichannels protects mice against tumour necrosis factor-induced inflammatory shock.
Tinneke Delvaeye,Maarten De Smet,Stijn Verwaerde,Elke Decrock,Aleksandra Czekaj,Roosmarijn E. Vandenbroucke,Kelly Lemeire,Amanda Gonçalves,Wim Declercq,Peter Vandenabeele,Dmitri V. Krysko,Luc Leybaert +11 more
TL;DR: Significant benefits of inhibiting connexin43 hemichannels are demonstrated to counteract TNF-induced SIRS-associated vascular permeability and lethality.
Journal ArticleDOI
Pannexin 1 Channels Contribute to IL-1β Expression via NLRP3/Caspase-1 Inflammasome in Aspergillus Fumigatus Keratitis
TL;DR: Pannexin 1 channels play important roles in the regulation of progression and leucocytes aggregation during corneal A. fumigatus infection via the NLRP3/Caspase-1/IL-1β pathway.
Journal ArticleDOI
Pannexin hemichannels: A novel promising therapy target for oxidative stress related diseases
Jin Xu,Linxi Chen,Lanfang Li +2 more
TL;DR: Pannexin hemichannels, novel therapeutic targets, hold promise in managing oxidative stress related diseases such as the tumor, inflammatory bowel diseases (IBD), pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), cardiovascular disease, insulin resistance (IR), and neural degeneration diseases.
Journal ArticleDOI
Endothelial pannexin 1-TRPV4 channel signaling lowers pulmonary arterial pressure in mice.
Zdravka Daneva,Matteo Ottolini,Yen Lin Chen,Eliska Klimentova,Maniselvan Kuppusamy,Soham A Shah,Richard D. Minshall,Cheikh I. Seye,Victor E. Laubach,Brant E. Isakson,Swapnil K. Sonkusare +10 more
TL;DR: In this paper, the authors showed that Panx1-P2Y2R-TRPV4 channel signaling, facilitated by caveolin-1, reduces PA contractility and lowers PAP in mice.
References
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Book ChapterDOI
Receptors for Purines and Pyrimidines
Vera Ralevic,Geoffrey Burnstock +1 more
TL;DR: In this review particular emphasis is placed on the discrepancy between the concentrations ofadenosine, ADP, and ATP in the purine receptors of UDP and UTP.
Journal ArticleDOI
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P Kubes,M Suzuki,D. N. Granger +2 more
TL;DR: Data suggest that endothelium-derived NO may be an important endogenous modulator of leukocyte adherence and that impairment of NO production results in a pattern ofLeukocyte adhesion and emigration that is characteristic of acute inflammation.
Journal ArticleDOI
Pannexin-1 mediates large pore formation and interleukin-1β release by the ATP-gated P2X7 receptor
TL;DR: Pannexin‐1, a recently described mammalian protein that functions as a hemichannel when ectopically expressed, is identified as this dye‐uptake pathway and signalling through pannexin•1 is required for processing of caspase‐1 and release of mature IL‐1β induced by P2X7 receptor activation.
Journal ArticleDOI
Intravascular danger signals guide neutrophils to sites of sterile inflammation.
Braedon McDonald,Keir Pittman,Gustavo B. Menezes,Simon A. Hirota,Ingrid Slaba,Christopher C. M. Waterhouse,Paul L. Beck,Daniel A. Muruve,Paul Kubes +8 more
TL;DR: Dynamic in vivo imaging revealed a multistep hierarchy of directional cues that guide neutrophil localization to sites of sterile inflammation, and the underlying mechanisms of recruitment of neutrophils into injured tissue.
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