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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Purinergic Signaling in the Cardiovascular System.
TL;DR: The involvement of purinergic signaling in cardiovascular pathophysiology and its therapeutic potential are discussed, including heart failure, infarction, arrhythmias, syncope, cardiomyopathy, angina, heart transplantation and coronary bypass grafts, coronary artery disease, diabetic cardiopathy, hypertension, ischemia, thrombosis, diabetes mellitus, and migraine.
Journal ArticleDOI
TBK1 at the Crossroads of Inflammation and Energy Homeostasis in Adipose Tissue.
Peng Zhao,Kai in Wong,Xiaoli Sun,Shannon M. Reilly,Shannon M. Reilly,Maeran Uhm,Zhongji Liao,Yuliya Skorobogatko,Yuliya Skorobogatko,Alan R. Saltiel,Alan R. Saltiel +10 more
TL;DR: It is reported that the kinase uniquely controls energy metabolism, and a unique role for TBK1 in mediating bidirectional crosstalk between energy sensing and inflammatory signaling pathways in both over- and undernutrition.
Journal ArticleDOI
Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications
Luc Leybaert,Paul D. Lampe,Stefan Dhein,Brenda R. Kwak,Péter Ferdinandy,Eric C. Beyer,Dale W. Laird,Christian C. Naus,Colin R. Green,Rainer Schulz +9 more
TL;DR: It is concluded that peptide-based investigations have raised several new opportunities for interfering with connexins and their channels that may soon allow preservation of gap junction communication, inhibition of hemichannel opening, and mitigation of inflammatory signaling.
Journal ArticleDOI
Mechanisms of ATP Release by Inflammatory Cells
TL;DR: Key effector functions of inflammatory cells are regulated by purinergic signaling in acute and chronic diseases, making extracellular nucleotide release a promising target for the development of new therapies.
Journal ArticleDOI
ATP Release Channels.
TL;DR: Five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1), volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR) anion channel), and maxi-anion channels(MACs), and a discussion on the future implications of understanding these channels are summarized.
References
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Journal ArticleDOI
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
TL;DR: PANX1 is identified as a plasma membrane channel mediating the regulated release of find-me signals and selective plasma membrane permeability during apoptosis, and a new mechanism of PANX1 activation by caspases is identified.
Journal ArticleDOI
ATP Release Guides Neutrophil Chemotaxis via P2Y2 and A3 Receptors
Yu Chen,Ross Corriden,Yoshiaki Inoue,Linda Yip,Naoyuki Hashiguchi,Annelies S. Zinkernagel,Victor Nizet,Paul A. Insel,Wolfgang G. Junger +8 more
TL;DR: Human neutrophils release adenosine triphosphate from the leading edge of the cell surface to amplify chemotactic signals and direct cell orientation by feedback through P2Y2 nucleotide receptors, which provides signal amplification, controlling gradient sensing and migration of neutrophil.
Journal ArticleDOI
Life cycle of connexins in health and disease
TL;DR: This review will assess the current understanding of wild-type and selected disease-linked mutant connexin transport through the secretory pathway, gap-junction assembly at the cell surface, internalization and degradation.
Journal ArticleDOI
Pannexin membrane channels are mechanosensitive conduits for ATP
TL;DR: Pannexin 1 channels have a wide expression spectrum, they are of large conductance and permeant for ATP, and they are mechanosensitive, Hence, pannexins are candidates for the release of ATP to the extracellular space upon mechanical stress.
Journal ArticleDOI
Nitric oxide modulates microvascular permeability.
Paul Kubes,D. N. Granger +1 more
TL;DR: The results suggest that inhibition of NO production by vascular endothelium leads to a reversible increase in microvascular protein efflux that is mediated by both leukocyte-dependent and -independent mechanisms.
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