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
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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Journal ArticleDOI
Constitutive SRC-mediated phosphorylation of pannexin 1 at tyrosine 198 occurs at the plasma membrane.
Leon J. DeLalio,Marie Billaud,Claire A. Ruddiman,Scott R. Johnstone,Joshua T. Butcher,Abigail G. Wolpe,Xueyao Jin,T.C. Stevenson Keller,Alexander S. Keller,Thibaud Rivière,Miranda E. Good,Angela K. Best,Alexander W. Lohman,Leigh Anne Swayne,Silvia Penuela,Roger J. Thompson,Paul D. Lampe,Mark Y Yeager,Brant E. Isakson +18 more
TL;DR: The discovery of the YLK motif is contained within an SRC homology 2 domain and is directly phosphorylated by SRC proto-oncogene, nonreceptor tyrosine kinase (SRC) at Tyr198, which implicates SRC-mediated PANX1 function in normal vascular hemodynamics and suggests that Tyr198-phosphorylated PANx1 is involved in hypertensive vascular pathology.
Journal ArticleDOI
Connexins: Key Players in the Control of Vascular Plasticity and Function.
TL;DR: Channel-dependent and -independent roles of connexins in blood vessel function range from basic processes of vascular remodeling and angiogenesis to vascular permeability and interactions with leukocytes with the vessel wall.
Journal ArticleDOI
Endothelial Pannexin 1 Channels Control Inflammation by Regulating Intracellular Calcium.
Yang Yang,Yang Yang,Leon J. DeLalio,Angela K. Best,Edgar Macal,Jenna Milstein,Iona Donnelly,Ashley M. Miller,Martin W. McBride,Xiaohong Shu,Michael Koval,Brant E. Isakson,Scott R. Johnstone +12 more
TL;DR: The data in this study provide the first evidence, to the authors' knowledge, that [Ca2+]i regulation via the Panx1 channel induces a feed-forward effect on NF-κB to regulate IL-1β synthesis and release in endothelium during inflammation.
Journal ArticleDOI
P2X7 receptor-pannexin 1 interaction mediates extracellular alpha-synuclein-induced ATP release in neuroblastoma SH-SY5Y cells
Anna Wilkaniec,Magdalena Gąssowska,Grzegorz A. Czapski,Magdalena Cieślik,Grzegorz Sulkowski,Agata Adamczyk +5 more
TL;DR: It is concluded that purinergic receptors might be putative pharmacological targets in the molecular mechanism of extracellular ASN toxicity and interference with P2X7 signaling seems to be a promising strategy for the prevention or therapy of PD and other neurodegenerative disorders.
Journal ArticleDOI
Connexins and pannexins in vascular function and disease
TL;DR: This review provides an overview of current knowledge with respect to the pathophysiological role of these channels in large arteries, the microcirculation, veins, the lymphatic system and platelet function.
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.
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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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Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis
Faraaz B. Chekeni,Michael R. Elliott,Michael R. Elliott,Joanna K. Sandilos,Scott F. Walk,Scott F. Walk,Jason M. Kinchen,Jason M. Kinchen,Eduardo R. Lazarowski,Allison Armstrong,Allison Armstrong,Silvia Penuela,Dale W. Laird,Guy S. Salvesen,Brant E. Isakson,Douglas A. Bayliss,Kodi S. Ravichandran,Kodi S. Ravichandran +17 more