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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Localization and trafficking of Pannexin 1 in polarized and non-polarized cells
TL;DR: The data indicate that polarized trafficking of Panx1 does not depend upon the dileucine motif, and that the expression ofPanx1 mutants may play a role in dysregulating the epithelial cell phenotype.
Journal ArticleDOI
Amount of Pannexin 1 in Smooth Muscle Cells Regulates Sympathetic Nerve–Induced Vasoconstriction
TL;DR: In this paper , the authors used genetically modified mouse models enabling expression of Panx1 in vascular cells to be varied, and found that deletion of PANX1 in smooth muscle cells (SMCs) prevented constriction by electric field stimulation of sympathetic nerves.
Journal ArticleDOI
TNF-α Plus IL-1β Induces Opposite Regulation of Cx43 Hemichannels and Gap Junctions in Mesangial Cells through a RhoA/ROCK-Dependent Pathway
Narinder Sharma,S. N. Smirnov +1 more
TL;DR: In this article , the authors showed that activation of Cx43 hemichannels and inhibition of cell-cell coupling during pro-inflammatory conditions could contribute to oxidative stress and damage of mesangial cells via the RhoA/ROCK pathway.
Posted ContentDOI
Amount of Pannexin 1 in smooth muscle cells regulates sympathetic nerve induced vasoconstriction
TL;DR: In this article , the role of Panx1 in mediating constriction in response to direct sympathetic nerve stimulation is not known, and it is unknown how the expression level of PANX1 in SMCs influences a-adrenergic responses.
Posted ContentDOI
Platelet pannexin-1 channels modulate inflammation during abdominal aortic aneurysm formation
Lisa Maria Metz,T. Feige,Larissa de Biasi,Agnes Ehrenberg,Joscha Mulorz,Laura Mara Toska,Friedrich Reusswig,Christine Quast,Norbert Gerdes,Malte Kelm,Hubert Schelzig,Margitta Elvers +11 more
TL;DR: In this article , the authors analyzed the contribution of platelet Panx1 in the progression of abdominal aortic aneurysm (AAA) and detected enhanced platelet plasma levels in AAA 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.
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TL;DR: This Review focuses on new aspects of one of the central paradigms of inflammation and immunity — the leukocyte adhesion cascade.
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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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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