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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Journal ArticleDOI
Recent insights into endothelial control of leukocyte extravasation
TL;DR: Recent insights into endothelial signaling events that are linked to leukocyte migration across the vessel wall are reviewed and less-well-studied components in the endothelium that also control transendothelial migration are addressed that provide novel insights in the complexity associated with this process.
Journal ArticleDOI
Pannexin 1 activation and inhibition is permeant-selective
Brian Skriver Nielsen,Trine Lisberg Toft-Bertelsen,Sara Diana Lolansen,Connor L. Anderson,Morten Schak Nielsen,Roger J. Thompson,Nanna MacAulay +6 more
TL;DR: Ethidium permeability does not reflect equal permeation of other molecules and thus is no measure of general Panx1 activity and therefore cannot be extrapolated to its effects on the permeability of another molecules.
Posted ContentDOI
Brain Endothelial Cell TRPA1 Channels Initiate Neurovascular Coupling
Pratish Thakore,Michael G. Alvarado,Sher Ali,Amreen Mughal,Paulo W. Pires,Evan Yamasaki,Harry A. T. Pritchard,Harry A. T. Pritchard,Brant E. Isakson,Cam Ha T. Tran,Scott Earley +10 more
TL;DR: A role is established for endothelial TRPA1 channels as sensors of neuronal activity and show that they respond accordingly by initiating a vasodilatory response that redirects blood to regions of metabolic demand.
Journal ArticleDOI
Blockade of Pannexin-1 Channels and Purinergic P2X7 Receptors Shows Protective Effects Against Cytokines-Induced Colitis of Human Colonic Mucosa
Erica F. Diezmos,Irit Markus,Dayashan S. Perera,Steven Gan,Li Zhang,Shaun L. Sandow,Shaun L. Sandow,Paul P. Bertrand,Paul P. Bertrand,Lu Liu +9 more
TL;DR: The blockade of Panx1 and P2X7R reduced the inflammatory cytokines-induced crypt damage, loss of tight junctions and increase in cell permeability, and may have roles in causing mucosal damage, a common clinical feature of inflammatory bowel disease.
Journal ArticleDOI
Consideration of Pannexin 1 channels in COVID-19 pathology and treatment.
Leigh Anne Swayne,Scott R. Johnstone,Chen Seng Ng,Juan C. Sanchez-Arias,Miranda E. Good,Silvia Penuela,Alexander W. Lohman,Abigail G. Wolpe,Victor E. Laubach,X. Michael Koval,Brant E. Isakson +10 more
TL;DR: PANX1, and drugs known to target PANX1 (including the FDA-approved drug probenecid), should be the focus of further investigation in the context of SARS-CoV-2 infection and its associated pathology in COVID-19 patients.
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
Getting to the site of inflammation: the leukocyte adhesion cascade updated
TL;DR: This Review focuses on new aspects of one of the central paradigms of inflammation and immunity — the leukocyte adhesion cascade.
Journal ArticleDOI
Nitric oxide: an endogenous modulator of leukocyte adhesion.
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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